Dissertations / Theses: 'Phenotypic Spectrum'

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ANNUNZIATA, SILVIA. "Genetic and phenotypic characterization of Autism Spectrum Disorders." Doctoral thesis, Università degli studi di Pavia, 2022. http://hdl.handle.net/11571/1452943.

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Svärd, Louise. "Evaluation of phenotypic and genotypic extended-spectrum beta-lactamase detection methods." Thesis, Uppsala University, Department of Medical Biochemistry and Microbiology, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8021.

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The emergence and spread of resistance in Enterobacteriaceae is a growing concern in human medicine today. Enterobacteriaceae producing extended-spectrum β-lactamases (ESBLs) have become efficient at inactivating β-lactam antibiotics especially the newer third generation cephalosporins. In addition, ESBL producing Enterobacteriaceae are frequently resistant to other groups of commonly used non-β-lactam antibiotics such as the fluoroquinolones. Reliable, rapid and low cost methods to detect ESBLs in clinical microbiology laboratories are therefore required.The aim of this project was to evaluate the phenotypic and genotypic detection methods for ESBLs and to examine the optimum antimicrobial agent(s) for ESBL detection. A comparison with the CLSI susceptibility test and the ESBL screen test was performed using a number of clinical isolates of E. coli and Klebsiella spp. suspected to contain ESBLs. Two confirmatory tests, the double disc synergy test and the combination disc test for ESBLs were also compared. Single and multiplex PCR assays were established using primers for the TEM-, SHV- and OXA-type β-lactamases. The results of this study show that ESBL screening is required in routine laboratories for successful detection of ESBLs. The best indicator cephalosporin for detection of ESBLs in E. coli was cefpodoxime whilst the best indicators for detection of ESBLs in K. pneumoniae were cefpodoxime and ceftazidime. The combination disc confirmatory test demonstrated the highest rate of detection. The multiplex PCR assay was found to be a rapid and cost-effective method for ESBL detection. However, nucleotide sequencing is required to confirm ESBL production amongst these organisms.

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Mehta, Ameeta. "Phenotypic spectrum of patients with congenital disorders of the hypothalamo-pituitary axis." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1444891/.

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Mutations within the cascade of pituitary transcription factors that play a crucial role in its development and differentiation have improved our understanding of variable hypopituitarism in children. The diagnosis of hypopituitarism is problematic as it is dependent on a series of endocrine tests varying in sensitivity and specificity, compounded by evolving hormonal deficiencies. In order to test the hypothesis that human phenotypes are determined by the neuroanatomy which is further influenced by the position of the abnormal gene within the pituitary developmental cascade, clinical, biochemical, magnetic resonance MR imaging and molecular data were retrospectively analysed in subgroups from a cohort of 825 patients with variable hypothalamo-pituitary H-P abnormalities. The major aims were to determine abnormalities on MR imaging that help predict the spectrum of hypopituitarism, to assess if genotype determined phenotype and to ascertain the optimum test for diagnosis of hormone deficiency. Results showed good structure-function relationships within the H-P axis. Anterior pituitary hypoplasia and an undescended posterior pituitary were 6.7 and 33.1 times more prevalent in patients with hypopituitarism as compared with those without. These abnormalities were also significantly associated with endocrinopathies in patients with optic nerve hypoplasia. Within patients with hypopituitarism, midline forebrain defects MFD and pituitary stalk abnormalities were found to be significantly associated with combined pituitary hormone deficiency as opposed to isolated GH deficiency. GH was critical for early postnatal growth, which was also influenced by other pituitary hormones and MFD. Regular evaluation of serum thyroxine concentration best revealed TSH deficiency, as the TRH test was normal in 23% of patients with central hypothyroidism limiting its role as a diagnostic test. A combination of the short Synacthen test and 0800-hour serum Cortisol concentrations represented the optimal method of investigation for ACTH deficiency. The LHRH test in infancy needs careful interpretation, as responses were gender-specific with significantly exaggerated serum FSH concentrations in females. There was a poor genotype-phenotype correlation, particularly in patients with mutations in HESX1, PROP and SOX3, both within and between pedigrees, indicating a role for other genetic or environmental factors on phenotypic expression.

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Ibrahim, Delveen. "Phenotypic and genotypic study of multidrug resistant, extended spectrum β-lactamase (ESBL)-producing Escherichia coli isolated from a dairy farm". Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/46613/.

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Approximately 400 tonnes of antibiotics (including synthetic antibiotics) are used every year in treating infections in farm animals, and as prophylactics against infection. Antimicrobial resistance is a crucial problem that is now of great concern in public health, with food and food producing animals as a potential route for spread of these resistances, especially resistance to cephalosporins, which is increasing. The main aim of this study was to determine the prevalence and range of multidrug resistance (MDR) and extended spectrum β-lactamase (ESBL) or ampicillin C (AmpC) β-lactamase producing Escherichia coli within a commercial dairy farm, to understand the diversity of resistance to β-lactam antibiotics, and to determine if co-carriage of other antimicrobial resistance (AMR) was associated with ESBL/AmpC producers. This would allow a better understanding of the contributions that farms and farm slurry may make to the presence of AMR in the environment, and the reservoir of resistance in agriculture. In this study, E. coli strains were isolated from a single dairy farm (East Midlands, England, United Kingdom) on two visits, a preliminary isolation using TBX agar in 2012 and more targeted isolation using antibiotic supplemented TBX media in 2014. Confirmed E. coli (126 out of 155 selected strains) were genotyped using ERIC-PCR and analysis of the ERIC profiles showed that, in comparison to the 2014 isolates, the 2012 isolates were a quite distinct genetic population. Antimicrobial sensitivity tests were performed using a disk diffusion test for all the strains against 17 antimicrobials representing seven different antimicrobial groups: β-lactams, aminoglycosides, tetracyclines, sulphonamides, chloramphenicols, nitrofuran derivatives and quinolones. Antimicrobial resistance profiling showed 92% of isolates showed resistance to at least 1 antimicrobial, of which 27.8% of the isolates were isolated without antibiotic selection, and 57.9% of the isolates were multidrug resistant to between 3 and 15 antimicrobials, of which 43.6% of the isolates were isolated using antibiotic supplemented media. Two strains showed resistance to imipenem which appeared to be an unstable phenotype and was subsequently lost. The finding was unexpected and of concern as imipenem is not used in veterinary medicine. blaCTX-M, blaTEM and blaOXA genes were detected by PCR among the cephalosporin resistant strains. No plasmid ampC genes were detected. Four strains were fully sequenced and the genetic/genomic environment surrounding β-lactamase genes and analysis of some other AMR genes showed these genes are associated with transposable elements, such as ISEcp1, ISCR2, IS26-IS26, Tn2, Tn10 or within a class I integron carried by a Tn-21 like transposon. The association of AMR genes with these transposable elements might make the dissemination rate of these genes greater. Some of the insertion sequence-AMR gene combinations are thought to be novel, such as the unique insertion of ISEcp1- blaCTX_M14 unit into the fdeC chromosomal gene. This is the first study of this type performed on this dairy farm; the data showed a diverse range of resistance genes present in the E. coli population in the farm, including resistance to historically used antimicrobials as well as cephalosporins in contemporary use, and a high level of multidrug resistance. The spread of such highly resistant strains to the environment and possibly to humans could present a real threat to human health especially if they are pathogenic.

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Baiardi, Simone <1985&gt. "Effect of host genotype and prion strain on the phenotypic heterogeneity of Creutzfeldt-Jakob disease: the peripheral nervous system involvement and the spectrum of the genetic form." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amsdottorato.unibo.it/9097/1/baiardi_simone_tesi.pdf.

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The first study was designed to assess whether the involvement of the peripheral nervous system (PNS) belongs to the phenotypic spectrum of sporadic Creutzfeldt-Jakob disease (sCJD). To this aim, we reviewed medical records of 117 sCJDVV2, 65 sCJDMV2K, and 121 sCJDMM(V)1 subjects for symptoms/signs and neurophysiological data. We looked for the presence of PrPSc in postmortem PNS samples from 14 subjects by western blotting and real-time quaking-induced conversion (RT-QuIC) assay. Seventy-five (41.2%) VV2-MV2K patients, but only 11 (9.1%) MM(V)1, had symptoms/signs suggestive of PNS involvement and neuropathy was documented in half of the VV2-MV2K patients tested. RT-QuIC was positive in all PNS samples, whereas western blotting detected PrPSc in the sciatic nerve in only one VV2 and one MV2K. These results support the conclusion that peripheral neuropathy, likely related to PrPSc deposition, belongs to the phenotypic spectrum of sCJDMV2K and VV2, the two variants linked to the V2 strain. The second study aimed to characterize the genetic/molecular determinants of phenotypic variability in genetic CJD (gCJD). To this purpose, we compared 157 cases of gCJD to 300 of sCJD. We analyzed: demographic aspects, neurological symptoms/signs, histopathologic features and biochemical characteristics of PrPSc. The results strongly indicated that the clinicopathological phenotypes of gCJD largely overlap with those of sCJD and that the genotype at codon 129 in cis with the mutation (i.e. haplotype) contributes more than the latter to the disease phenotype. Some mutations, however, cause phenotypic variations including haplotype-specific patterns of PrPSc deposition such as the “dense” synaptic pattern (E200K-129M), the intraneuronal dots (E200K-129V), and the linear stripes perpendicular to the surface in the molecular layer of cerebellum (OPRIs-129M). Overall, these results suggest that in gCJD PRNP mutations do not cause the emergence of novel prion strains, but rather confer increased susceptibility to the disease in conjunction with “minor” clinicopathological variations.

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Carpita, Barbara. "INVESTIGATING BIOCHEMICAL MARKERS OF ADULT AUTISM SPECTRUM DISORDER PHENOTYPES." Doctoral thesis, Università di Siena, 2022. http://hdl.handle.net/11365/1194483.

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Background: Recently, in the framework of a dimensional approach to autism-related psychopathology, increasing attention has been paid on investigating specific features of Autism spectrum disorder (ASD) during adulthood. Particular interest was paid on milder forms of ASD, without intellectual and language impairment, which may remain under-detected in early life. Moreover, several reports highlighted the presence of significant autistic-like traits in non-affected first-relatives of subjects with ASD, leading to the conceptualization of a “Broad autism phenotype” (BAP). Despite an increasing body of data from neuroimaging studies reported neurostructural and neurofunctional alterations in BAP, there is still a lack of evidence about potential biochemical correlates of ASD-like traits. The first attempts in researching biochemical markers of ASD focused on neurotransmitters and in particular on serotonin (5-HT), reporting possible different alterations between adulthood and childhood and/or between different kinds of biological samples. Brain-derived neurotrophic factor (BDNF), tryptophan (TRP), and metabolites of the TRP-derived kynurenine (KYN) shunt were also found altered in ASD children, and authors hypothesized their possible involvement in increased excitotoxicity or inflammatory activity. Other research also reported immune system activation among ASD children: results in this field seem promising, with studies stressing an association of cytokine levels with different grades of clinical severity and specific clusters of symptoms. Moreover, altered homocysteine (HCY) metabolism and altered trans-sulfuration and methylation processes are acquiring growing interest as possible metabolic signatures of ASD. Despite that, for most of these parameters scant research focused on adult samples and/or on BAP, without studies comparing adult ASD patients with their adult relatives. Aims: The aim of this work was to identify possible biochemical correlates for sub-threshold and over-threshold ASD symptomatology in adults. In particular, the study aimed to: evaluate presence and features of ASD symptoms in adult ASD patients without language or intellectual impairment and their first-degree relatives, as well as in controls, through suitable psychometric scales; evaluate levels of various biochemical parameters, among the three groups, and in particular: circulating levels of 5-HT, TRP, KYN, quinolinic acid (QA), chinurenic acid (KYNA), BDNF, IL-6, HCY; evaluate the possible correlations between clinical features, as measured by the psychometric scales, and biochemical parameters. Methods: A sample of adult ASD patients (ASD group) and first-degree relatives of the ASD probands (BAP group) were recruited among patients followed at the Psychiatric Section of Azienda Ospedaliera Universitaria Pisana, whereas unrelated controls (CTL group) were recruited on a voluntary basis. All subjects underwent a psychiatric and biochemical assessment. The psycometric instruments employed were: the Structured Clinical Interview for DSM-5, the Adult Autism Sub-threshold Spectrum (AdAS Spectrum), the Autism-Spectrum Quotient (AQ), the Ritvo Autism Asperger Diagnostic Scale,14-item version (RAADS-14), the Ruminative Response Scale (RRS) as well as the Work and Social Adjustment Scale (WSAS). A sample of peripheral venous blood was withdrawn from all the subjects and then processed for obtaining the different analytical specimen for biochemical assessment: the platelet poor plasma (PPP), platelet pellets and serum. All these parameters were measured by means of dedicated Enzyme-linked immunosorbent assay (ELISA) procedures. Results: ASD patients reported significantly higher total scores (greater severity of autistic traits/functional impairment) than the other groups on all psychometric scales. The BAP group reported intermediate scores, significantly higher than the CTL group. At the same time ASD patients reported significantly lower intra-platelet 5-HT, PPP 5-HT and TRP levels than BAP and CTL groups. Significant differences depending on pharmacological treatment within groups were reported for intra-platelet 5-HT levels only, and no difference in intra-platelet 5-HT was found when exluding subjects in treatment with antidepressants from the analysis. Moreover, significantly lower levels of KYNA were reported in both ASD and BAP group when compared with CTL subjects. IL-6 and HCY were instead significantly higher in the ASD group than in the CTL one, with BAP group showing intermediate levels, not significantly different from those reported in the other two groups. A multinomial logistic regression analysis identified higher levels of HCY and IL-6 as the statistically predictive variables of being in the ASD group, while increased IL-6 was statitstically predictive also of being in the BAP group. Specific patterns of association were found between autistic symptoms and biochemical variables. The biochemical parameters most associated with functional impairment were the increased levels of HCY and IL-6. Conclusions: our results confirm the need of further research on alterations of TRP metabolism in ASD and highlight the value of assessing the association of ASD with specific immune system alterations and impaired HCY-related metabolism, which may affect trans-sulfuration/methylation processes in this population. Moreover, our results confirm the presence of intermediate alterations in relatives of ASD patients also from a biochemical point of view, thus providing more support to the presence of a continuum between sub-threshold and full-threshold ASD phenotypes. Finally, our results stress the importance of evaluating metabolomics/proteomic signatures in the field of ASD patients’ care and management.

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Purcell, Deborah. "Development of rapid methods for the characterisation of sugarcane phenotypes." Thesis, Queensland University of Technology, 2003. https://eprints.qut.edu.au/105692/1/T%28S%29%20431%20Development%20of%20rapid%20methods%20for%20the%20characterisation%20of%20sugarcase%20phenotypes.pdf.

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The Australian Sugar Industry has an export market reputation as a supplier of good quality raw sugar. Maintaining this good quality reputation is paramount and the industry relies on a set of sugar quality parameters to do so. This research offers a more efficient method of screening for one particular parameter. At present, a rating for each sugarcane variety with respect to beverage floc (a visible defect, which manifests itself in soft drink that has been standing for some time) is established using extensive field trials. This problem of beverage floc is caused by the production in the field of a bacterial polysaccharide that has the ability to scavenge or cause aggregation of other low concentration impurities, which leads to the production of beverage floc. Using data generated by the gas chromatographic (GC) analysis of sugarcane stalk wax a phenotypic association was observed between the chemical composition of stalk wax and the varietal floc rating. This relationship was determined by applying chemometric methods of principal component analysis (PCA) where groups of variables were identified according to resistance and susceptibility. The partial least squares (PLS) approach was used for predicting ratings, which fall within the accepted variation of traditional methods. Spectroscopic methods were utilised in order to further develop the potential of this correlation. This initial work involves predominantly Photo-Acoustic Spectroscopy (PAS) and Near Infrared Spectroscopy (NIR). These results are preliminary but never the less very encouraging, with further development and validation a non-destructive wax analysis which can be performed in the field and allow the processing of potentially hundreds and perhaps thousands of varieties on a reasonable timescale. The result will enable a more informed decision to be made about a particular variety if one of the quality parameters is known earlier in the breeding program. In addition, more plants will be screened and this will increase the genetic pool used to identify desirable genetic traits, which can be incorporated into the plant-breeding program.

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Tang, Shan. "Expanding the phenotype and genetic spectrum of myoclonic astatic epilepsy." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/expanding-the-phenotype-and-genetic-spectrum-of-myoclonic-astatic-epilepsy(991de1f3-e1a5-49d7-b68a-43abb859fb39).html.

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Myoclonic astatic epilepsy (MAE) is a rare generalised childhood epilepsy with variable but poorly described neurodevelopmental outcome. Family studies suggest a major genetic influence as up to two thirds of relatives have seizures, or electroencephalographic (EEG) abnormalities. MAE is associated with 10 different genes, yet these genes account for less than 20% of the genetic aetiology of MAE leaving the majority unexplained. The aims of this thesis were (1) describe the epilepsy and neurodevelopmental phenotype of MAE cases, (2) perform EEG studies on first degree family members for familial EEG abnormalities and compare occurrence of epileptiform features to population prevalence and (3) to collect DNA and identify MAE causative genetic variants through exome sequencing. I assembled the largest MAE cohort (n=123) to date. The epilepsy phenotype is remarkably similar to previously published cohorts. I identified a severe neurodevelopmental phenotype: intellectual disability was reported in 64.9%, autism spectrum disorder in 21.3% and attention deficit hyperactivity symptoms in 41.0%. Additionally, extremely low adaptive behavioural scores were identified in 69.4% of cases. I performed EEG studies on 38 first-degree relatives of 13 MAE families, and found an excess of epileptiform EEG features in adults (>16 years), compared to controls (P=0.05, RR 6.82). I identified likely pathogenic or candidate variants in 11 of 109 cases. This comprised known genes associated with MAE: CHD2 n=1, SYNGAP1 n=2, SLC6A1 n=1, KIAA2022 n=1; epilepsy associated genes novel for MAE: KCNB1 n=1, MECP2 n=1, KCNH5 n=1, and three new candidate genes; SMARCA2 n=1, ASH1L n=1 and CHD4 n=1. Lastly, I highlight phenotypic features which help correlate with known and novel specific gene associations, discuss that MAE is a phenotypic and genetic nosological bridge between genetic generalised epilepsy and epileptic encephalopathy, and discussion applications and future directions leading on from this project.

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Eleftheriades, Amelia L. "Theory of mind, central coherence and executive function in parents of children with autistic spectrum disorder." Thesis, University of East Anglia, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246968.

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Introduction: This study investigates cognitive theory of autistic spectrum disorder. Based on the argument that the disorder may have a genetic component to its aetiology, cognitive characteristics similar to those associated with the condition are hypothesised to be evident in the parents. Theory of mind, central coherence and executive function are therefore investigated. Relationships between these three areas of cognitive function are also explored. Methodology: Nineteen parents of children with high functioning autism or Asperger syndrome were compared with 18 gender-matched parents of normally developing children, on measures of theory of mind, central coherence, and executive function. Results: Executive function was significantly poorer in the parents of children with autistic spectrum disorder, than in the control group; but theory of mind and central coherence were similar across the two groups. Overall, 52.6 % of the autism group and only 5.6 % of the control group fell below age and IQ weighted cut-off scores on the Hayling and Brixton tests of executive dysfunction, A number of significant correlations between test measures were found. Discussion : These findings provide further support for the genetic argument and the executive function theory of autism, but fail to support the theory of mind or central coherence models. Possible interpretations of the significant associations between test scores were considered in the light of previous findings. Methodological issues were considered important. Limits of the executive dysfunction model as a stand-alone theory of autistic spectrum disorder were also highlighted. Ideas regarding clinical relevance and future research were discussed.

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Hofvander, Björn. "AD/HD and autism spectrum disorders in adults." Malmö : Forensic Psychitry, Lund University, 2009. http://www.lu.se/o.o.i.s?id=12588&postid=1487259.

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Kamara, Dana Eliya. "Characterizing the Sleep Phenotype in 16p11.2 Deletion and Duplication." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1590253282112184.

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Riendeau, Noémie. "Autism spectrum disorders : identification of novel microdeletions and microduplications and their associated phenotypes." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/13850.

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Background: Autism Spectrum Disorders (ASDs) are common, heritable neurobiologic conditions of unknown etiology confounded by significant clinical and genetic heterogeneity. In recent years, array CGH technology has been used to rapidly screen the genome for pathogenic copy number variants (PCNVs) associated with ASDs and data from 6 studies suggests that PCNVs contribute to ASD pathogenesis in 6-27% of cases. However, the role of PCNVs in ASDs remains poorly understood, due to the absence of comprehensive phenotyping of ASD subjects. Methods: To address this, we collected detailed clinical, medical, physical and morphologic information on all subjects and investigated whether these phenotypes would be good indicators of PCNV risk. We studied somatic phenotypes, as opposed to behavioural indices that change over time and with treatment, in an attempt to provide better evidence for the biological/embryological origin of ASDs and help define new ASD syndromes. Results: Seven disease-specific and potentially pathogenic CNVs were uncovered in 6/40 patients (15%). Two changes were de novo and 5 were inherited from normal parents, but had never been reported in normal populations before. All PCNVs were discovered in individuals without family history of autism, ranged in sizes from 175kb to 2.5Mb, and revealed 9 good candidate genes. Our results suggest that whilst no single phenotypic feature investigated associates with PCNV risk, there is an indication that the presence of phenotypic abnormalities involving multiple body areas may be a better indicator of PCNVs in ASDs than the presence or number of minor physical anomalies alone. In addition, our findings lend support to the idea that complex autism, involving significant dysmorphology, is etiologically distinct from essential autism, with an increased prevalence of ID, seizures and health problems, and a higher proportion of individuals without family history of ASDs. Conclusion: We identified novel areas of chromosomal imbalance associated with ASDs and provide detailed phenotypic information for every subject for which these new PCNVs were detected. The extensive phenotyping of affected individuals carrying clinically relevant CNVs is needed in order to understand their role in the etiology of autism and ultimately provide earlier and more reliable means for ASD diagnosis and treatment.

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Maddox, Brenna Burns. "The Broad Autism Phenotype in the General Population: Evidence Through Eye-Tracking." Thesis, Virginia Tech, 2012. http://hdl.handle.net/10919/76960.

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The broad autism phenotype (BAP) has been defined both behaviorally and biologically. There has been little research on the association of the BAP, behaviorally defined, with neural or cognitive biomarkers typically associated with Autism Spectrum Disorder (ASD). People diagnosed with ASD tend to show reduced gaze fixation toward the eye region, but much less eye-tracking research has been done related to the BAP (Boraston & Blakemore, 2007). In this study, we sought to assess eye gaze patterns in people with the behaviorally defined BAP, as defined by a score of 30 or above on the Autism Spectrum Quotient (AQ; Baron-Cohen et al., 2001). It was hypothesized that the BAP group participants would exhibit longer average fixation duration to the eye region during an emotion recognition condition, relative to a free-viewing condition, whereas the comparison group participants (defined as an AQ score of 24 and below) would not show a difference in fixation duration to the eye region between conditions. Nine hundred and thirty-nine undergraduates completed an online survey, and 45 of these students (15 BAP group and 30 comparison group) participated in the eye-tracking session, where they viewed a series of human faces, each presented twice within a condition. Results revealed a significant negative relationship between social anxiety and eye region fixation duration in the free-viewing condition, for both presentations of faces. Contrary to expectation, BAP predicted longer eye region fixation duration in the free-viewing condition, for the second presentation of faces. Possible explanations for these surprising findings are discussed. Master of Science

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Everroad, Richard Craig. "Diversification of marine picocyanobacteria : the ecology and evolution of spectral phenotype and phycoerythrin /." view abstract or download file of text, 2007. http://proquest.umi.com/pqdweb?did=1324371891&sid=1&Fmt=2&clientId=11238&RQT=309&VName=PQD.

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Thesis (Ph. D.)--University of Oregon, 2007. Typescript. Includes vita and abstract. Includes bibliographical references (leaves 117-137). Also available for download via the World Wide Web; free to University of Oregon users.

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Dakh, Farshid. "Mutation frequency of non-ESBL phenotype SENTRY (Asia-Pacific) isolates of Klebsiella pneumoniae conversion to an ESBL positive phenotype." Thesis, Queensland University of Technology, 2008. https://eprints.qut.edu.au/28413/1/Farshid_Dakh%27s_Thesis.pdf.

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Extended spectrum β-lactamases or ESBLs, which are derived from non-ESBL precursors by point mutation of β-lactamase genes (bla), are spreading rapidly all over the world and have caused considerable problems in the treatment of infections caused by bacteria which harbour them. The mechanism of this resistance is not fully understood and a better understanding of these mechanisms might significantly impact on choosing proper diagnostic and treatment strategies. Previous work on SHV β-lactamase gene, blaSHV, has shown that only Klebsiella pneumoniae strains which contain plasmid-borne blaSHV are able to mutate to phenotypically ESBL-positive strains and there was also evidence of an increase in blaSHV copy number. Therefore, it was hypothesised that although specific point mutation is essential for acquisition of ESBL activity, it is not yet enough, and blaSHV copy number amplification is also essential for an ESBL-positive phenotype, with homologous recombination being the likely mechanism of blaSHV copy number expansion. In this study, we investigated the mutation rate of non-ESBL expressing K. pneumoniae isolates to an ESBL-positive status by using the MSS-maximum likelihood method. Our data showed that blaSHV mutation rate of a non-ESBL expressing isolate is lower than the mutation rate of the other single base changes on the chromosome, even with a plasmid-borne blaSHV gene. On the other hand, mutation rate from a low MIC ESBL-positive (≤ 8 µg/mL for cefotaxime) to high MIC ESBL-positive (≥16 µg/mL for cefotaxime) is very high. This is because only gene copy number increase is needed which is probably mediated by homologous recombination that typically takes place at a much higher frequencies than point mutations. Using a subinhibitory concentration of novobiocin, as a homologous recombination inhibitor, revealed that this is the case.

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Dakh, Farshid. "Mutation frequency of non-ESBL phenotype SENTRY (Asia-Pacific) isolates of Klebsiella pneumoniae conversion to an ESBL positive phenotype." Queensland University of Technology, 2008. http://eprints.qut.edu.au/28413/.

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Extended spectrum β-lactamases or ESBLs, which are derived from non-ESBL precursors by point mutation of β-lactamase genes (bla), are spreading rapidly all over the world and have caused considerable problems in the treatment of infections caused by bacteria which harbour them. The mechanism of this resistance is not fully understood and a better understanding of these mechanisms might significantly impact on choosing proper diagnostic and treatment strategies. Previous work on SHV β-lactamase gene, blaSHV, has shown that only Klebsiella pneumoniae strains which contain plasmid-borne blaSHV are able to mutate to phenotypically ESBL-positive strains and there was also evidence of an increase in blaSHV copy number. Therefore, it was hypothesised that although specific point mutation is essential for acquisition of ESBL activity, it is not yet enough, and blaSHV copy number amplification is also essential for an ESBL-positive phenotype, with homologous recombination being the likely mechanism of blaSHV copy number expansion. In this study, we investigated the mutation rate of non-ESBL expressing K. pneumoniae isolates to an ESBL-positive status by using the MSS-maximum likelihood method. Our data showed that blaSHV mutation rate of a non-ESBL expressing isolate is lower than the mutation rate of the other single base changes on the chromosome, even with a plasmid-borne blaSHV gene. On the other hand, mutation rate from a low MIC ESBL-positive (≤ 8 µg/mL for cefotaxime) to high MIC ESBL-positive (≥16 µg/mL for cefotaxime) is very high. This is because only gene copy number increase is needed which is probably mediated by homologous recombination that typically takes place at a much higher frequencies than point mutations. Using a subinhibitory concentration of novobiocin, as a homologous recombination inhibitor, revealed that this is the case.

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Feldman, Benjamin H. "Face Processing in the Broad Autism Phenotype: Exploring Face Processing as an Endophenotype of Autism Spectrum Disorder." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1427815061.

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Thacker, Stetson Thomas. "An Exploration of the Molecular Pathogenesis of the Autism Component of PTEN Hamartoma Tumor Syndrome (PHTS): Towards an Understanding of PTEN Variation on PHTS Phenotype Diversity." Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1614788701475458.

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Johansson, Maria. "Autism syndromes in three behavioural phenotype conditions : a clinical psychiatric study of 76 individuals with Möbius sequence, CHARGE syndrome, and oculo-auriculo-vertebral spectrum /." Göteborg : Institute of Neuroscience and Physiology, Child and Adolescent Psychiatry, Göteborg University, 2007. http://hdl.handle.net/2077/3306.

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Norris, Megan. "Examining the Autism Phenotype: The Structure of Autism Spectrum Disorders as Measured by the Autism Diagnostic Observation Schedule." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1281709680.

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Petrone, Paola. "Design and optimization of a computer-assisted tool for erythrocyte phenotyping: in search of a new biomarker for autism spectrum disorders." Doctoral thesis, Università di Siena, 2022. http://hdl.handle.net/11365/1213174.

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The morphology of a red blood cell (RBC) in physiological conditions (discocyte) is of primary importance for its main physiological role (i.e., the transport of respiratory gases to and from the tissues). The erythrocyte membrane-cortical cytoskeleton-complex structure, ensuring both shape resilience and marked physiological deformability, also allows erythrocytes to undergo peculiar shape changes, from spherical globes (spherocytes), concave shapes (stomatocytes), cells provided with spines (echinocytes) or with a central crest (knizocytes). Several pathological conditions are associated with characteristic RBC shape alterations. For instance, typical thorny red cells (acanthocytes) are prevalent in neuroacanthocytosis, a group of rare genetic diseases; hereditary spherocytosis, elliptocytosis, and stomatocytosis are RBC disorders resulting from mutations in genes encoding various membrane and skeletal proteins; codocytes are a common occurrence in beta- thalassemia. Furthermore, aberrant erythrocytic shapes are observed in renal and liver disease, and in case of hemoglobinopathies and toxemias. Leptocytes, as well as other abnormal erythrocyte shapes, are reported in patients diagnosed with Rett syndrome, an X-linked genetically determined neurodevelopmental disorder. Abnormal RBC shapes have been described also in patients diagnosed with autism spectrum disorders (ASD). ASD represent a complex set of neurodevelopmental disorders, characterized by social and behavioral impairments. These disorders have a prevalent genetic etiology; however, epigenetically acting environmental factors (e.g., immune dysregulation, pollutants) seem to play a key role in the development of the disease. This condition is associated with a high social impact and strong suggestions of a dramatically rising prevalence in the general pediatric population over the last decades. In the present thesis work, we started to investigate the potential value of the RBC shape as a biomarker candidate for an early ASD diagnosis, illustrating and discussing the results achieved so far within this broad research project. One of these results is the optimization of a new protocol, based on the acupuncture method, for blood samples preparation aimed at SEM (Scanning Electron Microscopy) morphological analysis of RBC. Indeed, to reach the final research goal it is necessary to carry out many bloods drawn from young children in a practical way. The novel preparation and imaging method, both minimally invasive and cheap, consists in aspirating by a capillary tube (preloaded with anticoagulant solution) a drop of peripheral blood obtained from a prick in a human subject’s fingertip. Samples are subsequently processed by ad hoc protocols and imaged at SEM. Another goal successfully achieved through this work is the favorable opinion and approval from local ethics committee. Preliminary results from blood samples analysis at SEM confirm the presence of morphologically abnormal erythrocytes in ASD patients in a greater extent than in healthy volunteers. Nevertheless, given the small sample size searched to date, more accurate information and a high caseload of subjects are still needed. The last and most consistent part of this thesis work illustrates development and validation of a new computer-assisted tool for erythrocyte phenotyping in SEM micrographs. Indeed, achieving our final research goal involves the analysis of many blood samples, each of which needing a time-consuming manual search, count and classification of a large number of RBC. In this context a software capable to semi-automatically associate a distribution of erythrocytes among the relevant morphological classes to each examined patient would represent a powerful tool towards a more rapid and reproducible analysis of RBC morphology. Furthermore, observations from studying of intra-operator variability of the manual RBC morphological analysis by SEM carried out in this thesis work suggest the need of a high number of replicate counts, supporting the key relevance of implementing reliable computer-assisted algorithms and machine learning systems for our research project. Our own software, developed using Microsoft Visual Studio 2010 as a working environment and the C++ language as a programming language, has shown to be able to detect RBC in SEM micrographs and to intercept erythrocyte morphological categories, albeit with different degrees of efficiency. This new software represents a promising and powerful tool with many potential applications, from early ASD diagnostic to basic research in hematology. This thesis work presents the initial phases of an ambitious research project about erythrocyte morphological changes in pediatric ASD patients, laying solid foundations for its continuation. Indeed, further investigations are needed to establish the statistical significance of the differences about erythrocyte morphological alterations in blood micro-samples from ASD patients and neurotypical controls. Moreover, our work will continue validating the data - obtained by our software - about the distribution of erythrocytes among several morphometric classes in SEM micrographs from peripheral blood samples. These aspects are of seminal importance in the research aimed at discovering potential novel biomarkers for ASD diagnosis based on the SEM analysis of peripheral blood micro-samples.

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Wong, Dana. "Theory of mind and executive function impairments in autism spectrum disorders and their broader phenotype : profile, primacy and independence." University of Western Australia. School of Psychology, 2004. http://theses.library.uwa.edu.au/adt-WU2004.0066.

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Impairments in both theory of mind (ToM; the ability to attribute mental states to oneself and others) and executive function (EF; a group of high-level cognitive functions which help guide and control goal-directed behaviour) have been demonstrated in individuals with autism spectrum disorders (ASDs). Both deficits have been proposed by different groups of researchers as being the single primary cognitive deficit of autism, which can subsume the other deficit as secondary or artefactual. However, few studies have examined the nature of the relationship between ToM and EF in ASDs or conducted a systematic investigation of their relative primacy. This research principally sought to establish the primacy and independence of impairments in ToM and EF in ASDs and thereby evaluate the validity of single versus multiple primary deficit models of autism. These aims were addressed in two studies, both broad in scope. The first study was an investigation of the profile, primacy, and independence of ToM and EF impairments in individuals with ASDs. The sample included 46 participants with ASDs and 48 control participants matched on age and non-verbal ability. The profile of impairments was examined by measuring ToM and a range of EF components using tasks employing, wherever possible, process-pure indices of performance. Primacy was measured by focussing on i) whether or not the deficits observed were universal among individuals with ASDs; ii) whether the deficits were able to discriminate individuals with ASDs from matched controls (i.e., predict group membership); and iii) the ability of ToM and EF deficits to explain the full range of autistic symptomatology, as measured by correlating cognitive performances with behavioural indices. The relationship between ToM and EF impairments was investigated by conducting correlations between ToM and EF variables as well as analysing the incidence of dissociations between impairments in the two domains. The ASD group was found to demonstrate significant impairments in ToM and several components of EF including planning, verbal inhibition, working memory (in a context where inhibitory control was required), and both verbal and non-verbal generativity. However, neither ToM nor EF impairments were able to meet all of the criteria for a primary deficit in ASDs. EF deficits were found to be more primary, but could not account for ToM as a secondary deficit, as ToM and EF were found to be independent (i.e., uncorrelated and dissociable) deficits in the ASD group. This pattern of results suggested that a multiple deficits model involving at least two independent impairments appeared to best characterise ASDs, but the data were compatible with several variants of such a model (e.g., involving distinct subtypes versus a multidimensional spectrum). The second study was an investigation of ToM and EF impairments in siblings of individuals with ASDs, who have previously been found to demonstrate a subclinical “broad autism phenotype”. The main aims of this study were i) to identify whether ToM or EF deficits could meet criteria for an “endophenotype” or vulnerability marker for the autism genotype in unaffected relatives, which would have further implications about the primacy of ToM and EF in ASDs; and ii) to further investigate the validity of various multiple deficits models of ASDs by examining the pattern of ToM and EF performance in those showing the broad phenotype. Participants were 108 siblings of individuals with ASDs and 67 siblings of controls, tested on the same ToM and EF tasks used in the first study. Confirming the superior primacy of EF deficits found in Study One, there was no significant difference in ToM performance between ASD and control siblings, but ASD siblings showed weaknesses on two measures of EF. Furthermore, there appeared to be different subgroups of siblings demonstrating different cognitive profiles, consistent with the heterogeneity evident in the first study. This research indicated that ASDs cannot be explained by a single primary cognitive deficit. These findings hold important theoretical and empirical implications and highlight further questions about which type of multiple deficits model might best explain ASDs.

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Best, Catherine. "The boundaries of the cognitive phenotype of autism : social cognition and central coherence in young people with autistic traits and their first degree relatives." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/1846.

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Autism is a behaviourally defined disorder. The impairments in social communication and repetitive behaviours are individually non-specific. The disorder has indistinct boundaries both with other psychiatric disorders and with normal personality types. At the cognitive level, groups of people with autistic disorder can be differentiated from people without the disorder by their ability to reason about beliefs and knowledge (Theory of Mind) and by tests of visual disembedding (central coherence). This study examined whether young people with some of the behavioural features of autism but not necessarily a diagnosis, would show this distinctive cognitive profile. In a sample of 60 young people with additional learning support needs, we found that those with high levels of autistic traits (n=40) showed the same cognitive profile as has been found in people diagnosed with autistic disorder. This supports the view that autism is an extreme on a continuum of cognitive traits. Given the highly heritable nature of autism, we hypothesised that the parents of the young people with autistic traits will also display these cognitive features. The results indicated that there was no difference between the groups of parents on an advanced test of social cognition. Parents of people with high autistic traits were more resistant to one of the visual illusions and saw fewer reversals of an ambiguous figure when IQ was statistically controlled. These results in a sample with a low genetic load suggest ambiguous figures will be important in delineating the broader cognitive phenotype of autism.

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Cassel, Tricia D. "Examination of the Communicative Deficits Associated with the Broad Phenotype of Autism in Infant Siblings of Children with Autism Spectrum Disorders." Scholarly Repository, 2008. http://scholarlyrepository.miami.edu/oa_dissertations/129.

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Infants with older siblings on the autism spectrum (ASD-sibs) are at risk for socio-emotional difficulties. ASD-sibs were compared to children of typically developing siblings (TD-sibs) in the Face-to-Face/Still-Face (FFSF) at 6 months and the Early Social Communication Scales (ESCS) at 8, 10, 12, 15, and 18 months. ASD-sibs exhibited non-significant trends to smile less and display more neutral affect than TD-sibs during the FFSF. There was a significant status by gender interaction such that male ASD-sibs showed less smiling and lower affective valence compared to male TD-sibs. Additionally, ASD-sibs showed a lack of emotional continuity in the FFSF. ASD-sibs displayed less initiating joint attention, initiating behavioral requesting, and responding to joint attention over time than TD-sibs. Results are discussed with respect to the social orienting model of autism.

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Maruani, Anna. "Exploration de l'hétérogénéité phénotypique des Troubles du Spectre Autistique." Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/MARUANI_Anna_2_va_20181123.pdf.

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Les troubles du spectre autistique (TSA) sont définis par des déficits persistants dans la communication sociale et l'interaction sociale ainsi que par l’aspect restreint et répétitif des comportements et des intérêts. Cette entité recouvre des situations cliniques très hétérogènes, tant par le spectre de sévérité des symptômes que par la variété des comorbidités et des signes associés. Si l’étiologie génétique semble prépondérante, les mécanismes impliqués sont complexes et hétérogènes. Une stratégie possible pour décomposer cette hétérogénéité consiste à s’appuyer sur l’étude des relations phénotype-génotype et de façon plus large sur l’étude de sous-groupes phénotypiques comme les particularités sensorielles, les comorbidités ou les particularités neuro-anatomiques, afin de définir des catégories plus homogènes. L’objectif de la thèse a été d’explorer de façon multimodale l’hétérogénéité de ces troubles. La première partie de ma thèse a porté sur l’exploration des relations phénotype-génotype. La première étude a porté sur l’exploration du syndrome de Jacobsen (JS, délétion en 11q24.2-25) caractérisé par une déficience intellectuelle (DI) et un risque plus élevé de TSA. Dans cette région critique 11q24.2-25, nous avons supposé que l’haplo-insuffisance de la Neurotrimine (NTM) (molécule d'adhésion cellulaire neuronale) pourrait augmenter le risque de TSA et pourrait affecter les volumes des structures du cerveau. Si au final, NTM n’a pu être incriminé comme gène de susceptibilité pour les TSA, les explorations ont fourni de nouvelles informations sur l'impact de la délétion 11q24.2-25 sur l'anatomie du cerveau. En effet, en utilisant la segmentation automatique nous avons exploré la macrocéphalie chez un patient porteur d’une grande délétion de novo touchant NTM et présentant un phénotype clinique de JS : nous avons observé, chez ce patient, un volume accru de structures sous-corticales mais une diminution de la matière grise occipitale. La deuxième étude a porté sur les gènes CNTN5 et CNTN6 qui codent des molécules d'adhésion cellulaire neuronale des voies neuronales sensori-motrices. Les investigations cliniques des patients porteurs de variants délétères de CNTN5 et/ou CNTN6 ont montré que ces patients étaient hypersensibles aux sons et que leurs potentiels évoqués auditifs (PEAs) montraient des changements dans les temps de latence. Ces résultats apportent une nouvelle lumière sur les gènes en lien avec les particularités sensorielles dans les TSA. Je présenterai enfin les résultats préliminaires d’une troisième étude, de liaison, chez une famille multiplexe avec TSA et synesthésie. Dans, la deuxième partie de la thèse j’exposerai une étude exploratoire dans laquelle nous avons émis l'hypothèse que les concentrations plasmatiques abaissées de mélatonine observées chez nos patients TSA (vs contrôles et apparentés) pourraient être liées à une diminution du volume de la glande pinéale (VGP). Les VGP ont été mesurés avec une méthode de mesure volumétrique à base de voxel à partir de l’imagerie par résonance magnétique (IRM). Pour mieux comprendre la relation entre le VGP et les taux de mélatonine plasmatique dans notre population, nous avons généré un modèle normatif. Le déficit en mélatonine semblait plus lié au statut du sujet vis à vis du TSA qu’au VGP. Cette étude nous a conduit à faire l’hypothèse que les variations de la mélatonine dans les TSA pourraient être principalement causées par la dérégulation de la voie de la mélatonine. En conclusion, l’ensemble de ces travaux montre l’importance d’une approche multimodale pour la compréhension des TSA pour ouvrir de nouvelles pistes en terme de stratégie thérapeutique Autism Spectrum Disorder (ASD) are defined by persistent deficits in social communication and social interaction as well as by the restricted and repetitive nature of behaviors and interests. This entity covers very heterogeneous clinical situations, as much by the spectrum of severity of symptoms as by the variety of comorbidities and associated signs. If the genetic etiology seems preponderant, the mechanisms involved are complex and heterogeneous. One possible strategy to break down this heterogeneity is to rely on the study of phenotype-genotype relationships and more broadly on the study of phenotypic subgroups such as sensory peculiarities, co-morbidities or neuro-anatomical peculiarities, in order to to define more homogeneous categories. The aim of the thesis was to explore multi-modally the heterogeneity of these disorders.The first part of my thesis focused on the exploration of phenotype-genotype relationships. The first study focused on the exploration of Jacobsen syndrome (JS, 11q24.2-25 deletion) characterized by intellectual disability (ID) and a higher risk of ASD. In this critical region 11q24.2-25, we hypothesized that haploinsufficiency of neurotrimin (NTM) (neuronal cell adhesion molecule) may increase the risk of ASD and may affect volumes of brain structures. In the end, NTM could not be incriminated as a susceptibility gene for ASD, but the explorations provided new information on the impact of the 11q24.2-25 deletion on brain anatomy. Indeed, using automatic segmentation we explored macrocephaly in a patient with a large NTM deletion with NTM and a clinical phenotype of JS: we observed an increased volume of subcortical structures in this patient. But a decrease in the occipital gray matter. The second study focused on the CNTN5 and CNTN6 genes that encode neuronal cell adhesion molecules of the sensory-motor neural pathways. Clinical investigations of patients with deleterious variants of CNTN5 and / or CNTN6 showed that these patients were hypersensitive to sound and that their auditory evoked potentials (ABRs) showed changes in latency. These results shed new light on genes related to sensory peculiarities in ASDs. I will present the preliminary results of a third linkage study in a multiplexed family with TSA and synesthesia.In the second part of the thesis, I will expose an exploratory study in which we hypothesized that the lowered plasma concentrations of melatonin observed in our ASD patients (vs controls and related) could be related to a decrease in the volume of the pineal gland (PGV). The PGV were measured with a voxel-based volumetric measurement method from magnetic resonance imaging (MRI). To better understand the relationship between VGP and plasma melatonin levels in our population, we generated a normative model. The melatonin deficiency seemed more related to the subject's status with respect to ASD than to VGP. This study led us to hypothesize that melatonin variations in ASD may be mainly caused by deregulation of the melatonin pathway.In conclusion, all of this work shows the importance of a multimodal approach for understanding ASD to open new avenues in terms of therapeutic strategy

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Harris, Tegan Maree. "B-lactamase-mediated resistance to antimicrobials : the relationship between genotype and phenotype." Thesis, Queensland University of Technology, 2014. https://eprints.qut.edu.au/77835/1/Tegan_Harris_Thesis.pdf.

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This thesis examined the ability to predict the emergence of bacteria resistant to antibiotics using genetic markers in the bacteria. Bacteria containing the genetic markers were able to become resistant to antibiotics, whereas bacteria that did not have the genetic markers remained susceptible. Existing techniques can identify the presence of resistance by looking at the characteristics of the bacteria during growth. However, having the ability to predict antibiotic resistance before it emerges could improve the preservation of currently available antibiotics and minimise treatment failure.

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Lundström, Samuel. "Beyond The Frame : A Literature Review of Sex Differences and Female Specific Expressions of Autism Spectrum Disorder." Thesis, Högskolan i Gävle, Socialt arbete, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-36708.

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Autism Spectrum Disorder (ASD) is a neuro-developmental diagnosis that occurs around four times more often in males compared to females. Most of what is known about ASD, as well as diagnostic criteria and screening tools are therefore based on male expressions. Little is known if females differ from males and how female specific expressions of ASD looks like. The aim of this study is therefore to investigate the explanations of the male bias and increase the understanding of these sex differences and female expressions of ASD. My research provides a systematic review of 35 articles that has examined these areas. By conducting a thematic analysis I found that females and males diagnosed with ASD in general show similar expressions but that there is small evidence for female specific expressions. By using the theory of gender stereotyping I am discussing these results and argue that research in the area is caught in a looping effect. The reviewed articles use predominantly male samples while researching sex differences and are therefore reproducing the male bias. Because the stereotypical male expressions persist, females need to express more severe symptoms in order to be detected and correctly diagnosed. I suggest that by increasing the number of female participants in research, the female expression of ASD will be better understood which can aid social workers to detect and provide adequate support and interventions for females. Autismspektrumtillstånd (AST) är en utvecklingsrelaterad neuro-diagnos som förekommer fyra gånger så ofta hos män som hos kvinnor. Det mesta av den nuvarande kunskapen om ASD samt diagnoskriterier och screening-verktyg är därför baserade på manliga uttryck. Huruvida kvinnor skiljer sig från män och hur kvinnliga uttryck ser ut är fortfarande relativt outforskat. Min studies syfte är att undersöka den manliga snedfördelningen som finns i diagnosen för att öka förståelsen för könsskillnader och kvinnliga ASD uttryck. Detta sker genom en systematisk forskningsöversikt av 35 artiklar som avhandlar nämnda områden. Genom att genomföra en tematisk analys fann jag att kvinnor och män överlag uppvisar liknande uttryck men att det trots det finns bevis för vissa kvinnospecifika uttryck. Jag belyser dessa resultat vidare genom en teori om könsstereotyper och argumenterar för att forskningen på området är fast i en looping-effekt. Då de granskade artiklarna använder övervägande manliga forskningsobjekt när de utforskar könsskillnader så återskapas den manliga snedfördelningen. På grund av detta så fortlever den stereotypiska manliga bilden vilket gör att kvinnor behöver uppvisa starkare symptom för att bli upptäckta och få en korrekt diagnos. Jag föreslår därför att forskningen ökar antalet kvinnliga deltagare så att kvinnliga ASD-uttryck kan bli bättre förstådda vilket kan hjälpa professionella i socialt arbete and enklare upptäcka och bistå med adekvata interventioner och stödprogram för dessa kvinnor.

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Stansfield, Jillian. "Alannah, Bree and CASSIE: The ABC of girls on the Autism Spectrum in early years classrooms." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2020. https://ro.ecu.edu.au/theses/2376.

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The prevalence of children diagnosed with autism spectrum disorder in classrooms is an increasingly common phenomenon in schools in Australia and in many other countries. While there is increasingly growing literature on how autistic boys manage and are managed in schools, little is known about the learning needs of girls on the autism spectrum. One reason offered for this imbalance of literature is that fewer girls are diagnosed than boys, as their presentations may differ. As girls on the autism spectrum are an underdiagnosed phenotype, it is little wonder that teachers do not have adequate knowledge or strategies to support girls in the classroom. The shortage of research evidence on autistic girls in the education context is one reason why girls are missing out on vital supports and understanding in the classroom due to the lack of knowledge and resources available to teachers. This, in turn, means teachers are underprepared to teach girls on the autism spectrum. One of the main aims of this study was to develop knowledge and theory about girls on the autism spectrum and their diverse learning needs in the early years of schooling, to provide further support to teachers and their students with an autism diagnosis and those who are yet to be diagnosed. This qualitative, in-depth case study explored the learning experiences of two girls on the autism spectrum in early years classrooms, to develop knowledge and theory on autistic girls’ varied behaviours and characteristics and how they can be best supported. Key ideas emerged throughout the cross-case analysis and were categorised under six themes: Communication, Academic, Social, Sensory, Identity and Encircle. Encircle further encompassed four areas: Challenges, Intervention, Professional Development and Classroom Strategies. Each area overlaps one another and impacts the key themes for every student on the autism spectrum. From this process, the CASSIE tool was developed to identify girls on the autism spectrum in the early years classroom and assist teachers to better manage their learning and social experiences. Development of CASSIE was the principal outcome, a teaching tool and resource for teachers to understand how girls on the autism spectrum learn and help them develop strategies for these students to reach their potential in the classroom. The CASSIE tool will not only benefit teachers and parents, but the wider support network of girls on the autism spectrum who are both diagnosed and undiagnosed. In doing so, it will shine a light on the learning needs of girls on the autism spectrum to ensure they are no longer invisible.

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Dor-Nedonsel, Emmanuelle. "Les schizophrénies précoces : épidémiologie, exploration clinique et neurocognitive, phénotypage de familles d'enfants avec schizophrénie et autisme." Thesis, Université Côte d'Azur (ComUE), 2017. http://www.theses.fr/2017AZUR4093/document.

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La schizophrénie précoce (SP), trouble rare (~0,01%) du neurodéveloppement est décrite sous deux formes : la schizophrénie très précoce, avant 13 ans et celle de l’adolescence entre 13 et 18 ans. Le diagnostic complexe à poser et les méconnaissances de la SP font supposer qu’elle est sous diagnostiquée et que les propositions thérapeutiques et de prise en charge sont encore peu spécifiques. Nous avons mené une première étude épidémiologique de prévalence pour : (1) évaluer le taux de sujets répondant au diagnostic de SP dans un échantillon de 302 enfants issus des structures médico-sociales et sanitaires en région PACA ; (2) caractériser sur le plan clinique et neurocognitif les enfants avec SP ; (3) évaluer le taux d’enfants répondant à la fois aux diagnostics de SP et de Troubles du Spectre Autistique (TSA). Puis, une deuxième étude, du sous-groupe d’enfants ayant une comorbidité SP et TSA, a exploré la psychopathologie, la personnalité et les capacités cognitives des membres du 1er degré des familles de ces enfants. Les résultats sont : un taux de 8,9% de patients avec SP, dont 59,3% de garçons âgés de 12,4 ans en moyenne (ET=3,2), avec un Quotient Intellectuel moyen de 72,5 (ET=21,4), des hallucinations (82,8%), des symptômes négatifs (70%), une comorbidité avec un TSA (41.2%) et des traitements neuroleptiques (51,5%). L’étude des familles a montré que les mères ont plus de troubles de la personnalité, de traits autistiques, de pathologies psychiatriques et un QI moyen plus faible. La constitution et le phénotypage de cette cohorte a permis dans les suites de ce travail, de lancer une étude génétique familiale avec séquençage d’exome des parents et des enfants avec SP Early Onset Schizophrenia (EOS), a rare neurodevelopmental disorder (≈0.01%) is categorized into two types: Very Early Onset Schizophrenia, before age 13 and Adolescent Schizophrenia between ages 13 and 18. This diagnosis is a difficult one to make and considering the lack of knowledge on EOS, we can presume that it is in fact under-diagnosed and that our treatment and management options are still not very specific. We conducted a first epidemiological prevalence study consisted in evaluating: (1) the rate of subjects with EOS diagnostic criteria among 302 children who receive care in psychosocial and sanitary care facilities in the PACA region; (2) the clinical and neurocognitive characteristics of those children with EOS; (3) the rate of children with both EOS and ASD criteria within the same sample. In a second study, focusing on a subgroup of children with comorbid EOS and ASD, we analyzed first-degree relatives from a psychopathological, personality and cognitive viewpoint. The results are: a high rate of patients (8.9%) with an EOS diagnosis, a male gender majority (59.3%), an average age of 12.4 (SD=3.2), an average intelligence quotient of 72.5 (SD=21.4), a rate of 82.8% of subjects with hallucinations, 70% with EOS negative symptoms, 41.2% with comorbid autism, and 51.5% with antipsychotic medications. The study of family members shows that mothers have a higher rate of personality disorders, autistic traits and psychiatric disorders, as well as a lower average IQ. The creation and the characterization of a phenotype of this cohort have led to a family-genetic analysis based on exome sequencing in the parents and children with EOS following this study

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Aslan, Hatice. "Using remote sensing in soybean breeding: estimating soybean grain yield and soybean cyst nematode populations." Thesis, Kansas State University, 2015. http://hdl.handle.net/2097/18830.

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Master of Science Department of Agronomy William T. Schapaugh Remote sensing technologies might serve as indirect selection tools to improve phenotyping to differentiate genotypes for yield in soybean breeding program as well as the assessment of soybean cyst nematode (SCN), Heterodera glycines. The objective of these studies were to: i) investigate potential use of spectral reflectance indices (SRIs) and canopy temperature (CT) as screening tools for soybean grain yield in an elite, segregating population; ii) determine the most appropriate growth stage(s) to measure SRI’s for predicting grain yield; and iii) estimate SCN population density among and within soybean cultivars utilizing canopy spectral reflectance and canopy temperature. Experiment 1 was conducted at four environments (three irrigated and one rain-fed) in Manhattan, KS in 2012 and 2013. Each environment evaluated 48 F4- derived lines. In experiment 2, two SCN resistant cultivars and two susceptible cultivars were grown in three SCN infested field in Northeast KS, in 2012 and 2013. Initial (Pi) and final SCN soil population (Pf) densities were obtained. Analyses of covariance (ANCOVA) revealed that the green normalized vegetation index (GNDVI) was the best predictive index for yield compared to other SRI’s and differentiated genotype performance across a range of reproductive growth stages. CT did not differentiate genotypes across environments. In experiment 2, relationships between GNDVI, reflectance at single wavelengths (675 and 810 nm) and CT with Pf were not consistent across cultivars or environments. Sudden death syndrome (SDS) may have confounded the relationships between remote sensing data and Pf. Therefore, it would be difficult to assess SCN populations using remote sensing based on these results.

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Endres, Renata Giuliani. "O fenótipo ampliado do autismo em pais e mães de crianças com transtorno do espectro do autismo." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2013. http://hdl.handle.net/10183/157642.

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A presença de traços de personalidade em familiares de pessoas com diagnóstico de Transtornos do Espectro do Autismo (TEA) parece corresponder a algumas das características comportamentais de indivíduos com TEA, apontando para a alta herdabilidade dessa condição. Esta área de estudos é referida como aquela que investiga o fenótipo ampliado do autismo (FAA). A presente pesquisa é composta por dois estudos: o primeiro teve como objetivo apresentar uma revisão crítica da literatura, especialmente sobre os aspectos comportamentais ligados ao FAA, abordando-se os traços de personalidade e diferenças de gênero, nos genitores. O segundo investigou a presença desses traços em genitores de crianças com o diagnóstico de TEA, através de um delineamento de estudos de casos múltiplos, utilizando instrumentos nacionais e internacionais. Os resultados apontam para a presença de traços autísticos nos genitores, especialmente em relação à área de Interação Social Recíproca e Comportamentos Repetitivos e Estereotipados. Esta pesquisa alinha-se a outras, ao identificar alguns traços de personalidade em pais e mães de crianças com autismo, que parecem corresponder, em algum nível, aos encontrados no TEA e, por isso, podem representar o fenótipo ampliado do autismo. The presence of personality traits in relatives of people diagnosed with Autism Spectrum Disorder (ASD) seems to correspond to some of the behavioral characteristics of individuals with ASD, pointing to the high heritability of this condition. This area of study is referred to as one that investigates the Broader Autism Phenotype (BAP). This research consists of two studies: one aimed at reviewing the literature, especially on the behavioral aspects related to the BAP, approaching the personality traits and gender differences in parents of children with autism. Second, we investigated the presence of these traits in these parents through a design of multiple case studies, using national and international measures. The results indicate the presence of autistic traits in these parents, especially in relation to the area of Social Interaction and Repetitive and Stereotyped Behaviors. This research aligns to other studies of the field, to identify some personality traits in parents of children with autism, which seem to correspond to some degree, those found in ASD and therefore may represent the broader autism phenotype.

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Herzer, Martina [Verfasser], Peter J. K. [Akademischer Betreuer] Freisinger, and Thomas Alois [Akademischer Betreuer] Meitinger. "Clinical spectrum and phenotype-genotype correlations in patients with mitochondrial complex I deficiency / Martina Herzer. Betreuer: Peter J. K. Freisinger. Gutachter: Thomas Alois Meitinger ; Peter J. K. Freisinger." München : Universitätsbibliothek der TU München, 2015. http://d-nb.info/1079001816/34.

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Dor-Nedonsel, Emmanuelle. "Les schizophrénies précoces : épidémiologie, exploration clinique et neurocognitive, phénotypage de familles d'enfants avec schizophrénie et autisme." Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2017. http://theses.univ-cotedazur.fr/2017AZUR4093.

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La schizophrénie précoce (SP), trouble rare (~0,01%) du neurodéveloppement est décrite sous deux formes : la schizophrénie très précoce, avant 13 ans et celle de l’adolescence entre 13 et 18 ans. Le diagnostic complexe à poser et les méconnaissances de la SP font supposer qu’elle est sous diagnostiquée et que les propositions thérapeutiques et de prise en charge sont encore peu spécifiques. Nous avons mené une première étude épidémiologique de prévalence pour : (1) évaluer le taux de sujets répondant au diagnostic de SP dans un échantillon de 302 enfants issus des structures médico-sociales et sanitaires en région PACA ; (2) caractériser sur le plan clinique et neurocognitif les enfants avec SP ; (3) évaluer le taux d’enfants répondant à la fois aux diagnostics de SP et de Troubles du Spectre Autistique (TSA). Puis, une deuxième étude, du sous-groupe d’enfants ayant une comorbidité SP et TSA, a exploré la psychopathologie, la personnalité et les capacités cognitives des membres du 1er degré des familles de ces enfants. Les résultats sont : un taux de 8,9% de patients avec SP, dont 59,3% de garçons âgés de 12,4 ans en moyenne (ET=3,2), avec un Quotient Intellectuel moyen de 72,5 (ET=21,4), des hallucinations (82,8%), des symptômes négatifs (70%), une comorbidité avec un TSA (41.2%) et des traitements neuroleptiques (51,5%). L’étude des familles a montré que les mères ont plus de troubles de la personnalité, de traits autistiques, de pathologies psychiatriques et un QI moyen plus faible. La constitution et le phénotypage de cette cohorte a permis dans les suites de ce travail, de lancer une étude génétique familiale avec séquençage d’exome des parents et des enfants avec SP Early Onset Schizophrenia (EOS), a rare neurodevelopmental disorder (≈0.01%) is categorized into two types: Very Early Onset Schizophrenia, before age 13 and Adolescent Schizophrenia between ages 13 and 18. This diagnosis is a difficult one to make and considering the lack of knowledge on EOS, we can presume that it is in fact under-diagnosed and that our treatment and management options are still not very specific. We conducted a first epidemiological prevalence study consisted in evaluating: (1) the rate of subjects with EOS diagnostic criteria among 302 children who receive care in psychosocial and sanitary care facilities in the PACA region; (2) the clinical and neurocognitive characteristics of those children with EOS; (3) the rate of children with both EOS and ASD criteria within the same sample. In a second study, focusing on a subgroup of children with comorbid EOS and ASD, we analyzed first-degree relatives from a psychopathological, personality and cognitive viewpoint. The results are: a high rate of patients (8.9%) with an EOS diagnosis, a male gender majority (59.3%), an average age of 12.4 (SD=3.2), an average intelligence quotient of 72.5 (SD=21.4), a rate of 82.8% of subjects with hallucinations, 70% with EOS negative symptoms, 41.2% with comorbid autism, and 51.5% with antipsychotic medications. The study of family members shows that mothers have a higher rate of personality disorders, autistic traits and psychiatric disorders, as well as a lower average IQ. The creation and the characterization of a phenotype of this cohort have led to a family-genetic analysis based on exome sequencing in the parents and children with EOS following this study

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Alvari, Gianpaolo. "Fine-Grained Analyses of Early Autism-related Social Behavior in Real-World Scenarios by Machine Learning." Doctoral thesis, Università degli studi di Trento, 2022. http://hdl.handle.net/11572/331002.

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Autism Spectrum Disorder (ASD) is a condition that carries high costs for families and the healthcare system, requiring extensive management both in terms of diagnosis and treatment. The implementation of AI-based systems in clinical practice represents a possible supportive solution that can help clinicians by providing more systematic meth- ods to monitor child behavior. The main advantage over more traditional observational approaches is to offer quantitative and refined analysis solutions that can be ecological at the same time. The relevance of AI in clinical applications can have a role both in the challenge of early detection and in designing intervention programs better tai- lored to the specific functioning of children with ASD. The research project presented in this dissertation focused on developing AI-based systems for fine-grained analysis of autism-related social behaviors and their validation in concrete clinical environments. Specifically, in Chapter 2, our first study is presented, which targets on implementing a computational phenotyping system to address the need for new early markers of the condition. Through fine-grained analytics of facial dynamics in videos, we identified a set of features that distinguished young (6-12 months) infants with ASD (18 ASD, 15 non-ASD) during unconstrained at-home interactions. In Chapters 3 and 4, we introduce EYE-C, a Behavior Imaging model for robust analysis of eye contact episodes in eco- logical therapist-child interactions. The system was validated in the clinical setting for personalized early intervention. First, we investigated the influence of extracted features in categorizing spectrum heterogeneity across a sample of 62 preschool (<6 years) chil- dren with ASD. Further, we tested our metrics as predictors of early intensive treatment outcomes in a sub-sample of 18 subjects with ASD. The project aims to demonstrate the feasibility of effective computational systems that are robust to the high variability of unstructured interactions, with emphasis on the applicative value in real-world scenar- ios. Even though based on limited sample sizes, the work presented may offer interesting insights into the perspective of integrating AI into clinical practice. The research project was funded by an FBK scholarship and developed in a double in- ternship at ODFLab (University of Trento) and the FBK Data Science for Health (DSH) research unit.

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Bourgeon, Marie-Aure. "Conception et évaluation d'un dispositif d'imagerie multispectrale de proxidétection embarqué pour caractériser le feuillage de la vigne." Thesis, Dijon, 2015. http://www.theses.fr/2015DIJOS066/document.

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En Viticulture de Précision, l’imagerie multi-spectrale est principalement utilisée pour des dispositifs de télédétection. Ce manuscrit s’intéresse à son utilisation en proxidétection, pour la caractérisation du feuillage. Il présente un dispositif expérimental terrestre mobile composé d’un GPS, d’une caméra multi-spectrale acquérant des images visible et proche infrarouge, et d’un Greenseeker RT-100 mesurant l’indice Normalized Difference Vegetation Index (NDVI). Ce système observe le feuillage de la vigne dans le plan de palissage, en lumière naturelle. La parcelle étudiée comporte trois cépages (Pinot Noir, Chardonnay et Meunier) plantés en carré latin. En 2013, six jeux de données ont été acquis à différents stades phénologiques.Pour accéder aux propriétés spectrales de la végétation, il est nécessaire de calibrer les images en réflectance. Cela requiert l’utilisation d’une mire de MacBeth comme référence radiométrique. Lorsque la mire est cachée par les feuilles, les paramètres de calibration sont estimés par une interpolation linéaire en fonction des images les plus proches sur lesquelles la mire est visible. La cohérence de la méthode d’estimation employée est vérifiée par une validation croisée (LOOCV).La comparaison du NDVI fournie par le Greenseeker avec celui déterminé via les images corrigées permet de valider les données générées par le dispositif. La polyvalence du système est évaluée via les images où plusieurs indices de végétation sont déterminés. Ils permettant des suivis de croissance de la végétation originaux offrant des potentialités de phénotypage ou une caractérisation de l’état sanitaire de la végétation illustrant la polyvalence et le gain en précision de cette technique Mutispectral imaging systems are widely used in remote sensing for Precision Viticulture. In this work, this technique was applied in the proximal sensing context to characterize vine foliage. A mobile terrestrial experimental system is presented, composed of a GPS receiver, a multi-spectral camera acquiring visible and near infrared images, and a Greenseeker RT-100 which measures the Normalized Difference Vegetative Index (NDVI). This optical system observes vine foliage in the trellis plan, in natural sunlight. The experimental field is planted with Chardonnay, Pinot Noir and Meunier cultivars in a latin squared pattern. In 2013, six datasets were acquired at various phenological stages.Spectral properties of the vegetation are accessible on images when they are calibrated in reflectance. This step requires the use of a MacBeth colorchart as a radiometric reference. When the chart is hidden by leaves, the calibration parameters are estimated by simple linear interpolation using the results from resembling images, which have a visible chart. The performance of this method is verified with a cross-validation technique (LOOCV).To validate the data provided by the experimental system, the NDVI given by the Greenseeker was compared to those computed from the calibrated images. The assessment of the versatility of the system is done with the images where several indices were determined. It allows an innovative follow-up of the vegetative growth, and offering phenotyping applications. Moreover, the characterization of the sanitary state of the foliage prove that this technique is versatile and accurate

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Biarnés, Pérez Marc 1973. "Increased fundus autofluorescence, a biomarker of lipofuscin content, as a risk factor for the progression of geographic atrophy secondary to age-related macular degeneration." Doctoral thesis, Universitat Pompeu Fabra, 2014. http://hdl.handle.net/10803/318157.

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L’atròfia geogràfica (AG) és la variant avançada de la degeneració macular associada a l’edat seca i es caracteritza per la presència d’àrees d’atròfia de l’epiteli pigmentari de la retina (EPR) que creixen progressivament, amb pèrdua secundària dels fotorreceptors i la coriocapilar adjacents. Actualment és una condició sense tractament. L’acumulació de lipofuscina a l’EPR, visualitzable clínicament mitjançant l’autofluorescència del fons d’ull (AFU) com a zones d’elevada autofluorescència, ha estat vinculada a la progressió de l’AG en alguns estudis. De fet, s’han descrit certs patrons (“fenotips”) en l’AFU basats en la distribució d’hiperautofluorescència que s’han associat amb taxes específiques de progressió de la malaltia. En aquesta Tesi hem fet un estudi clínic prospectiu per simplificar la complexa classificació dels patrons d’AFU i avaluar el paper de la hiperautofluorescència, un biomarcador de la lipofuscina, en la progressió de l’AG. Geographic atrophy (GA) is the advanced form of dry age-related macular degeneration. It is characterized by large areas of retinal pigment epithelium (RPE) atrophy that grow progressively, with concomitant loss of photoreceptors and choriocapillaris. Currently, there is no treatment for this disorder. Lipofuscin build-up within the RPE, which is identifiable by fundus autofluorescence (FAF) as areas of increased autofluorescence, has been linked to GA progression in some studies. Actually, the distribution of hyperautofluorescence on FAF identified some patterns (“phenotypes”), which have been associated with specific rates of disease growth. We conducted a prospective clinical study to simplify the complex classification of FAF patterns and to determine the role of increased FAF, a biomarker of lipofuscin, in the progression of GA.

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Chiang, Andrew Hann. "Mechanisms Underlying Phenotypic Heterogeneity in Simplex Autism Spectrum Disorders." Thesis, 2021. https://doi.org/10.7916/d8-7rj8-dh25.

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Autism spectrum disorders (ASD) are a group of related neurodevelopmental diseases displaying significant genetic and phenotypic heterogeneity. Despite recent progress in ASD genetics, the nature of phenotypic heterogeneity across probands is not well understood. Notably, likely gene-disrupting (LGD) de novo mutations affecting the same gene often result in substantially different ASD phenotypes. We find that truncating mutations in a gene can result in a range of relatively mild decreases (15-30%) in gene expression due to nonsense-mediated decay (NMD), and show that more severe autism phenotypes are associated with greater decreases in expression. We also find that each gene with recurrent ASD mutations can be described by a parameter, phenotype dosage sensitivity (PDS), which characterizes the relationship between changes in a gene’s dosage and changes in a given phenotype. Using simple linear models, we show that changes in gene dosage account for a substantial fraction of phenotypic variability in ASD. We further observe that LGD mutations affecting the same exon frequently lead to strikingly similar phenotypes in unrelated ASD probands. These patterns are observed for two independent proband cohorts and multiple important ASD-associated phenotypes. The observed phenotypic similarities are likely mediated by similar changes in gene dosage and similar perturbations to the relative expression of splicing isoforms. We also identify patterns of developmental and cell type-specific expression that additionally contribute to the variability of several autism phenotypes.

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Rocha, Isabella da. "Analysis of the mutational spectrum of the F7 gene and phenotypic implications." Master's thesis, 2021. http://hdl.handle.net/10773/33594.

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Congenital factor VII deficiency (FVIID) is the most frequent of the rare autosomal recessive bleeding disorders, comprising a wide molecular spectrum that correlates with plasma FVII levels and sometimes a bleeding phenotype. Establishing clinical significance for a variant is essential for an efficient diagnosis resulting in better patient care. For this, the variants must be submitted to the same methodological analysis of variant classification according to the ACMG recommendations. In a cohort of 550 patients from central Portugal, diagnosed with FVII deficiency over a period of 20 years, between February 2001 and June 2021, at the Laboratory of Molecular Hematology - SHC/CHUC, data of the functional and molecular studies were analyzed. After evaluating the genotype-phenotype of the variants identified in the F7 gene, these were then reclassified according to the international guidelines of the ACMG. For some cases it was necessary to perform molecular analyzes using PCR, MLPA, and direct Sanger sequencing. 404 unrelated patients (probands) had FVII levels<60% when compared with healthy individuals. Individuals with FVII levels<1% showed variants in homozygosity and lethal cases have been described. We found some unusual cases such as a double heterozygous patient for partial deletion of F7 and F10. A total of 32 rare F7 variants were found in a group of 185 individuals with polymorphisms and pathogenic variants, the majority being missense. Of these 32 variants, eleven were considered new, i.e., not previously described. This study allowed prenatal diagnosis to be available when requested. All variants were reclassified according to the ACMG international guideline, where most are deemed pathogenic or likely pathogenic. It was concluded that all the information found in this study is of relevant importance to understand the genotype/phenotype factors that contribute to the development of the knowledge of FVII deficiency in the Portuguese population. This combination of procedures ensured a more efficient diagnosis: analyzing the severity of FVII deficiency with greater precision for a more effective therapeutic approach. A deficiência congénita de fator VII (FVIID) é o mais frequente dos distúrbios hemorrágicos autossómicos recessivos, compreendendo um amplo espectro molecular que se correlaciona com os níveis plasmáticos de FVII e, por vezes, um fenótipo de hemorragia. Estabelecer o significado clínico para uma variante é essencial para um diagnóstico eficiente resultando num melhor atendimento ao doente. Para isso, as variantes devem ser submetidas à mesma análise metodológica de classificação de variantes conforme as recomendações da American College of Medical Genetics and Genomics (ACMG). Num grupo de 550 pacientes do centro de Portugal, diagnosticados com a deficiência de FVII ao longo de um período de 20 anos, entre fevereiro de 2001 e junho de 2021, no Laboratório de Hematologia Molecular - SHC / CHUC, foram analisados dados dos estudos funcionais e moleculares. Após avaliado o genótipo fenótipo das variantes identificadas no gene F7, em seguida as mesmas foram reclassificadas de acordo com as guidelines internacionais ACMG. Para alguns casos em que se verificou ser necessário, as análises moleculares foram efetuadas por meio de PCR, MLPA e sequenciação direta de Sanger. Nesta grupo, 404 doentes não relacionados (propósitos) tiveram níveis de FVII<60% quando comparado com os indivíduos saudáveis. Os indivíduos com níveis FVII:c<1% apresentaram variantes em homozigotia e foram descritos alguns casos letais. Foram também encontrados alguns casos raros como o de um doente duplo heterozigótico para deleção parcial do F7 e F10. Um total de 32 variantes raras no F7 foram encontradas num grupo de 185 indivíduos com polimorfismos e variantes patogénicas, sendo a maioria missense. Destas 32 variantes, onze foram consideradas novas, i.e., não descritas previamente. Este estudo permitiu disponibilizar o diagnóstico pré-natal quando solicitado. Todas as variantes foram reclassificadas de acordo com as guidelines internacionais ACMG, onde a maioria foi considerada patogénica ou provável patogénica. Concluímos que todas as informações encontradas nesse estudo foram de importância relevante para compreender o genótipo/fenótipo destes doentes e, assim, elucidar e desenvolver o conhecimento sobre a deficiência do FVII da população em Portugal. Este conjunto de procedimentos possibilitou um diagnóstico mais eficiente: analisar a gravidade da deficiência do FVII com maior precisão para uma abordagem terapêutica mais eficaz. Mestrado em Bioquímica

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Breda, João Filipe Barbosa. "Autosomal recessive nanophthalmos : MFRP mutation and phenotypical spectrum." Master's thesis, 2011. http://hdl.handle.net/10316/31198.

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Trabalho de projecto de mestrado integrado em Medicina (Oftalmologia) apresentado à Faculdade de Medicina da Universidade de Coimbra Nanophthalmos is a rare congenital disorder of the eye, usually bilateral and symmetrical, characterized by a small eye, associated with shortened axial length (21mm or less), high corneal curvature, narrow iridocorneal angle, high hyperopia (ranging from +8.00 to +25.00) and excessive thickening of both choroidal and scleral layers. Mutations in the membrane-type frizzled related protein (MFRP) gene have been identified as the cause of classic non-syndromic Mendelian recessive nanophthalmos. We studied 12 individuals with nanophthalmos from eleven unrelated families (five males, seven females, ages between 5 and 78 years). Clinical phenotype was defined using spectral-domain OCT (for retinal anatomical assessment) and ORBscan (for corneal curvatures and CCT). Molecular analysis was performed to identify MFRP mutations and establish potential genotype-phenotype correlations. No genotype-phenotype correlations were identified with respect to retinal and corneal changes. There is considerable posterior segment variability and retinal changes don’t seem to have a genetic correspondence. Corneal changes are probably due to a corneal compensatory mechanism to minimize the final refractive error. Whether this fact is a result of direct genetic influence or a consequence of scleral structural changes (thicker than normal), remains to be clarified. A Nanoftalmia é uma doença congénita rara do olho, normalmente bilateral e simétrica, caracterizada por um olho pequeno, associado a um comprimento axial diminuído (21mm ou menos), curvatura corneana acentuada, ângulo iridocorneano estreito, hipermetropia grave (variando de +8.00 a + 25.00) e espessamento excessivo das camadas coróide e esclera. Mutações no gene membrane-type frizzled related protein (MFRP) foram identificadas como sendo a causa de nanoftalmia não-sindrómica autossómica recessiva. Estudámos 12 indivíduos com nanoftalmia de onze famílias independentes (cinco homens, sete mulheres, com idades compreendidas entre os 5 e 78 anos). O fenótipo clínico foi definido usando OCT (para análise anatómica da retina) e ORBscan (para obter as curvaturas corneanas e a espessura central da córnea). Foi efectuada análise molecular para identificar mutações no gene MFRP e estabelecer correlações genótipo-fenótipo. Não foram identificadas correlações genótipo-fenótipo relativamente às alterações quer da retina, como da córnea. Existe uma variabilidade considerável do segmento posterior e as alterações retinianas não parecem ter correspondência genética. As alterações observadas na córnea provavelmente resultam de um mecanismo compensatório para minimizar o erro refractivo final. Fica por esclarecer se este facto resulta de influências genéticas directas ou se é consequência das alterações estruturais da esclera (espessura maior que o normal)

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Alfardan, Jaffar Bressler Jan Caetano Raol. "Genotypic spectrum and genotype-phenotype correlation of trimethylaminuria." 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:1450285.

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Thesis (M.P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2008. Source: Masters Abstracts International, Volume: 46-05, page: 2641. Advisers: Jan Bressler; Raol Caetano. Includes bibliographical references.

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Chien, Yi-Ling, and 簡意玲. "Neurocognitive & Electrophysiological Phenotypes and Genetic Risk of Autism Spectrum Disorders." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/96804963834959200811.

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博士 國立臺灣大學 臨床醫學研究所 103 Autism spectrum disorders (ASD) are a group of severe, multi-factorial, life-long impairing childhood-onset neurodevelopmental disorders that begin in the first 2 years and throught the entire life. Although the high prevalence and high psychosocial impact of the illness, the research of its etiology faces critical stagnation and the effect of treatment nowadays seems far from satisfaction. Clinical and etiological heterogeneity composes of the most important challenges. This study aims to investigate (1) the neurocognitive and sensory phenotypes beyond the core symptoms of ASD; (2) electrophysological response in response to auditory and thermsl stimuli; (3) prenatal/perinatal risk factors and genetic risks. Compared to typically developing controls (TD), youths with ASD showed more severe attention deficits, hyperactive/impulsive symptoms, and oppositinal defiant behaviors, with more severe oppositional defiant behaviors in Asperger’s disorder than autistic disorder. Around 65.6% patients with autistic disorder and 79.3% patients with Asperger’s disorder fulfilled the diagnosis of attention deficit hyperacitivty disorder. Combined type was higher than inattentive type and hyperactive/impulsive type. In Connors’ Continuous Performance Test, both autistic disorder and Asperger’s disorder revealed focused attention and sustained attention deficits, while youths with autistic disorder had more impairment in focused attention and youths with Asperger’s disorder had poorer sustained attention. In visual memory tasks, youths with ASD had a wide range of visual memory impairments that were moderated by age and IQ, in support with temporal and frontal lobe dysfunction in ASD. Memory loading of the tasks, and involvement of spatial working memory may also influence the visual memory performance. Young adults with ASD demonstrated more sensory symptoms in daily life, including lower registration, more sensory sensitivity and sensory avoiding, while fewer sensation seeking behviors. In response to duration deviant auditory stimuli, individuals with ASD showed a shorter P3a peak latency; this parameter was associated with social awareness deficits in ASD. Besides, P3a peak amplitude to frequency deviant stimuli was correlated with sensory avoiding and patterns preoccupation in TD, while P3a peak latency may reflect sensory avoiding and attention to details in ASD. Combined duration and frequency P3a latency, as well as sensory sensitivity and sensation seeking, ASD could be differentiated from TD. In contact heat evoked potentails (CHEP), individuals with ASD had attenuated CHEP response to thermal stimuli, which were correlated with self-reported sensory and autistic symptoms, indicated that CHEP parameters are potential trait markers for perceptual disturbance in individuals with ASD. Reported pain in ASD was similar to that in TD, and was predicted by N2 peak latency, overall autistic symptom severity, and low registration. N2 latency can also predict sensory sensitivity and social emotion problems. Pre-/perinatal complications occurred more frequently in both ASD probands and their unaffected siblings compared to TD controls. Probands with ASD had a higher number of complications than siblings, which may be associated with more severe autistic symptoms. The presence of some factors was associated with more severe overall autistic symptoms and/or stereotyped behaviors, suggesting a role of pre-/perinatal factor in moderating phenotype expression of ASD. The WNT2 haplotype and DRB1 genotype were not only associated with autism diagnosis but also associated with autistic symptoms and neuropsychological function respectively. The mechanisms of the pathogenesis of ASD warrant further research.

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Yao, Shu-ting, and 姚舒婷. "Therapeutic Options for Bacteremia Caused by Extended-spectrum Cephalosporin-resistant Escherichia coli or Klebsiella pneumoniae without Extended-spectrum beta-lactamase Phenotype." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/73344288666753866863.

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碩士 國立成功大學 臨床藥學研究所 95 Background Extended-spectrum beta-lactamase (ESBL)-producing organisms become more and more prevalent not only in nosocomial, but also in community-acquired infections. Standard methods for ESBL phenotype detection had been established. A carbapenem or ciprofloxacin is recommended for infections caused by ESBL-producing organisms. However, there is no consensus for optimal therapeutic agents for extended-spectrum cephalosporin (ESC) resistant infections without the ESBL phenotype. Objective We aimed to evaluate therapeutic outcomes of bacteremia caused by ESC-resistant Escherichia coli or Klebsiella pneumoniae strains without ESBL phenotype treated by a 4th-generation cephalosporin or carbapenem . Method Design： A retrospective review of medical records. Subjective： Patients with bacteremia caused by E. coli and K. pneumoniae with a specific resistant phenotype from July 2003 to December 2006 at National Cheng Kung University Hospital were included. The specific resistant phenotype indicated the absence of ESBL phenotype, and resistance to one of 3rd-generation cephalosporins and susceptibility to 4th-generation cephalosporins and carbapenems. Only the fist episode of each patient was included in the analysis. Those younger than 16 years old or with incomplete medical records were excluded. Endpoint： Primary endpoint of the present study was the mortality rate at 14 days. Results During the study period, 163 patients had bacteremia due to non-ESBL and ESC-resistant organisms. The mortality rate at 14 days after onset was 18.4%, and at 30 days 24.5%. Forty-six patients were treated by 4th-gerenation cephalosporin monotherapy, 24 by carbapenem monotherapy, and 24 by other antibiotics. In baseline data, such as age, gender, underlying diseases, infection sources, risk factors or complications, there was no significant difference among three groups. However, the severity of acute illness, indicated by APACH II score, among patients treated by carbapenem monotherapy tended to be higher than that of those treated by 4th-gerenation cephalosporin monotherapy (P=0.15). The 14-day mortality rate of 4th-gerenation cephalosporin monotherapy was 2.2%, and in contrast that of carbapenem monotherapy was 16.7% (P=0.045). However, the 14-day mortality rates of two groups were not significantly different in patients with severe infections (i.e, APACH II scores ≥16) (P=0.15) or in multiple regression analysis (P=0.14). Conclusion For bacteremia caused by ESC-resistant E. coli or K. pneumoniae strains without ESBL phenotype, the therapeutic efficacy of 4th-gerneration cephalosporins as definitive therapy was not inferior to that of carbapenems.

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LIN, YA-LING, and 林雅齡. "Broader Autism Phenotype, Parental Stress, and Coping among Parents of Patients with Autism Spectrum Disorder." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/86z5uz.

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碩士 玄奘大學 應用心理學系碩士班 107 This study aims to understand the broader autism phenotype (BAP), as well as coping with parental stress among parents of patients with autism spectrum disorder (ASD). The first phase recruited 359 parents to complete internet self-report questionnaireson BAP and parental stress. A total of 226 parents of normal children and 133 parents of ASD patients completed Phase 1 study. During the second phase, the investigator conducted individual semi-structured interviews with four parents who have ASD children, respectively. The purpose of the second phase is to understand parenting experiences, as well as how they coped with parental stress. The results showed the following. First, parents of normal children and parents of ASD patients did not differ significantly in BAP. BAP is correlated with parental stress. However, parents of ASD patients had significantly higher parental stress than parents of normal children.Second, four parents who were interviewed reported similar experiences including the sense of helplessness when their children were diagnosed, the difficulty of obtaining resources at school, the invalidation of parenting practice by family members such as husbands or mother-in-law, and the benefits of communicating with school teachers and adjusting personal attitudes toward parenting experiences. Third, parents showed different approaches to children’s interpersonal problems. For example, parents of high BAP tended to advise their ASD children to comply with group regulations or seek help from teachers, while parents of low BAP tended to discuss and teach specific interpersonal issues with their children. Although they may have BAP and thus experience more parental stress,parents of patients with ASD may understand their children’s difficulties well and advise their children to follow useful protocols. This finding is something that is valuable but may be overlooked by many researchers. This study utilized quantitative and qualitative methods to compare BAP and parental stress among parents of patients with ASD and parents of normal children and to explore how parents coped with parental stress. Future research may apply multiple methods of data collection and specifically, focus on the parents of patients with ASD to understand their needs and resilience.

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Manuel, Ana Rute Carvalho Matos. "Phenotypical description of a subset of individuals with pten germline mutations, autism spectrum disorder and macrocephaly." Master's thesis, 2016. http://hdl.handle.net/10316/33355.

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Trabalho de revisão do 6º ano médico com vista à atribuição do grau de mestre (área científica de pediatria) no âmbito do ciclo de estudos de Mestrado Integrado em Medicina. Introdução. A Perturbação do Espetro do Autismo (PEA) é uma doença desafiante do neurodesenvolvimento, com uma profunda origem multifatorial e uma hereditariedade complexa. Estudar genes de suscetibilidade provada e trabalhar em endofenótipos clínicos é necessário para estabelecer correlações genótipo-fenótipo mais válidas. O PTEN é um gene supressor tumoral localizado no cromossoma 10q23.3. A inativação do PTEN resulta na sobrerregulação da via sinalizadora PI3K/AKT, que afeta múltiplos processos celulares. Além disso, o PTEN tem um papel essencial no desenvolvimento cerebral e, consequentemente, no comportamento social normal, onde uma regulação estreita da via PI3K/AKT/mTOR tem grande importância. Muitos estudos têm dado ênfase à ligação entre mutações no PTEN e crianças com PEA, défice intelectual ou atraso do desenvolvimento. Por essa razão, testar a existência de mutação no PTEN é importante em casos de PEA com macrocefalia. No presente estudo temos por objetivo relatar um subconjunto de três indivíduos com uma mutação no PTEN e ambas PEA e macrocefalia. Doentes e Métodos. Reportamos uma amostra constituída por três doentes caucasianos com PEA e macrocefalia que varia entre +3DP e +4DP. A PEA foi diagnosticada com base numa pontuação positiva para ambos ADI-R e ADOS, e preenchimento dos critérios do DSM-5. Além disso, realizou-se uma extensa avaliação clínica, incluindo um exame neurológico e uma avaliação funcional utilizando a Escala de Desenvolvimento Mental de Griffiths e a Escala do Comportamento Adaptativo de Vineland. Além da pesquisa de mutação no PTEN, foram realizados testes laboratoriais para excluir causas médicas. Resultados. Os nossos resultados demonstram uma significativa heterogeneidade fenotípica. Encontrámos três mutações no PTEN: uma variante missense c.737C>T (p.Pro246Leu) heterozigótica no exão 7, uma duplicação de novo no exão 6 c.493-?_634+?(2) e uma mutação missense c.359C>A (p.Ala120Glu) heterozigótica no exão 5. Os resultados da ressonância magnética mostraram várias anormalidades. Discussão. Encontrámos uma duplicação de novo no exão 6, que segundo o nosso conhecimento nunca foi descrita em doentes com PEA ou PHTS. A evidência clínica aponta fortemente para a patogenicidade desta variante. Os nossos resultados reforçam a complexidade multifatorial da PEA e a necessidade de identificar marcadores biológicos e endofenótipos específicos. A ressonância magnética também pode ser um instrumento importante na investigação destes doentes. Um regime multidisciplinar de vigilância do risco de cancro estendido à vida adulta tem grande importância em todos os casos de mutação no PTEN. Investigação adicional nos doentes com PEA com mutação conhecida no PTEN é necessária para perceber o potencial da terapêutica alvo nestas síndromes neurocomportamentais. Conclusão. Este relato de caso é concordante com investigação contemporânea da etiologia das síndromes do neurodesenvolvimento e acrescenta uma mutação de novo com valor clínico, ainda não descrita.Introduction. Autism Spectrum Disorder is a challenging neurodevelopmental disorder, with a profound multifactorial origin and a complex inheritance. Studying proven susceptibility genes and working on clinical endophenotypes are needed to define more valid genotype-phenotype correlations. PTEN is a tumour suppressor gene located on chromosome 10q23.3. Inactivation of PTEN results in upregulation of the PI3K/AKT signalling pathway, which affects multiple cellular processes. Besides, PTEN has an essential role in brain development, and thus in normal social behaviour, where tight control of the PI3K/AKT/mTOR pathway is of great importance. Multiple studies have emphasized a linkage between PTEN mutations and children presenting macrocephaly together with ASD, intellectual disability or neurodevelopmental delay. For that reason, PTEN mutation testing is a major consideration in cases of ASD and/or neurodevelopmental delay with macrocephaly. In the present study we aim to report a subset of three individuals with a PTEN germline mutation and both ASD and macrocephaly. Patients and Methods. We report a sample of three caucasian patients, with ASD and macrocephaly ranging from +3SD to +4SD. ASD was diagnosed based on a positive score for both ADI-R and ADOS, and fulfilment of DSM-5 criteria. Furthermore, all underwent an extensive clinical evaluation, including an intellectual and functional evaluations with Griffiths Mental Development Scale and Vineland Adaptive Behaviour Scale. Besides PTEN molecular analysis, laboratory tests to rule out medical causes were performed. Results. Our findings revealed significant phenotypical heterogeneity. Three PTEN mutations were found: a missense variant c.737C>T (p.Pro246Leu) heterozygous in exon 7, a de novo duplication in exon 6 c.493-?_634+?(2), and a missense mutation c.359C>A (p.Ala120Glu) heterozygous in exon 5. MRI showed several abnormalities. Discussion. We encountered a de novo duplication in exon 6, which to our knowledge has never been described in ASD or PHTS patients. Clinical evidence strongly points to the pathogenicity of this variant. Our results reinforce the multifactorial complexity of ASD, and the necessity to identify biological markers and specific endophenotypes. MRI can also be a helpful instrument in the investigation of these patients. A multidisciplinary cancer surveillance regimen extended to adulthood is of great importance in all cases of PTEN mutation. Additional research in ASD patients with known PTEN mutation aetiology is necessary to disclose the full potential of target therapeutics in this neurobehavioural syndrome. Conclusion. This case report is concordant with contemporaneous investigation on the aetiology of neurodevelopmental disorders and adds a de novo mutation with clinical value, not yet described.

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Carreira, Maria Inês da Conceição. "SHANK3 gene: Genotype-Phenotype relationship in a sample with Autism spectrum disorder and/or Intellectual Developmental Disability." Master's thesis, 2020. http://hdl.handle.net/10316/97689.

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Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina Introdução. O gene SHANK3 é uma variante genética rara que foi descrita na literatura como forte candidata à modelagem molecular da PEA. As mutações do SHANK3 levam a defeitos sinápticos e de circuitos que podem resultar em distúrbios do desenvolvimento neurológico, como a PEA e a síndrome de Phelan-McDermid (PMS). A PMS é causada por deleções 22q13.3 e é caracterizada por distúrbio global do desenvolvimento (GDD) ou distúrbio de incapacidade intelectual (IDD), fala ausente ou gravemente atrasada, hipotonia, dismorfismos leves e PEA ou comportamento autístico-like. No presente estudo, objetivamos adicionar a descrição genótipo-fenótipo em um subconjunto de três indivíduos com uma mutação na linha germinativa SHANK3.Pacientes e métodos. Fornecemos dados clínicos e genéticos detalhados de três pacientes com mutações no gene SHANK3: dois identificados com deleção e um com duplicação. Todos foram submetidos a uma avaliação clínica extensa, incluindo informações coletadas dos pais, testes de Entrevista de Diagnóstico para o Autismo Revisados (ADI-R) e Cronograma de Observação do Diagnóstico do Autismo (ADOS) para diagnóstico ou descartar ASD. Também foram realizados exames neurológicos, dismorfológicos e genética clínica. Além disso, foram realizadas avaliações intelectuais e funcionais com Griffiths Mental Development Scales e Vineland-II, respectivamente.Resultados. O paciente 1 possui uma deleção terminal do cromossomo 22 (q13.31q13.33), abrangendo 51 genes (incluindo o gene SHANK3) e o paciente 3 possui uma deleção intersticial, envolvendo parcialmente o gene SHANK3. Ambos os pacientes foram diagnosticados com PMS associado a GDD ou IDD. O paciente 2 foi diagnosticado com TEA e apresenta uma duplicação no final do cromossomo 22 (q13.33), envolvendo três genes: SHANK3, ACR, RABL2B.Discussão e conclusão. As nossas conclusões estão amplamente alinhadas com as relatadas em estudos anteriores. Além disso, nosso estudo mostrou que a haploinsuficiência do SHANK3 devido à deleção intersticial, interrompendo apenas o gene SHANK3, é suficiente para causar um conjunto de características associadas ao SPM, nomeadamente manifestações neurocomportamentais. Além disso, este caso destaca a hipótese de que talvez não apenas a haploinsuficiência do SHANK3 esteja associada ao ASD, mas também a superexpressão do SHANK3. Background. Autism spectrum disorder (ASD) is a complex and life-long neurodevelopmental disorder that has a strong genetic influence. SHANK3 gene is a rare genetic variant that has been described in the literature as a strong candidate for the molecular modelling of ASD. SHANK3 mutations leads to a synaptic and circuitry defects that may result in neurodevelopmental disorders, such as ASD and Phelan-McDermid Syndrome (PMS). PMS is caused by 22q13.3 deletions and it is characterized by global developmental disorder (GDD) or intellectual disability disorder (IDD), absent or severely delayed speech, hypotonia, mild dysmorphisms and ASD or autistic-like behaviour. In the present study we aim to add genotype-phenotype description in a subset of three individuals with a SHANK3 germline mutation.Patients and Methods. We provide a detail clinical and genetic data of three patients with SHANK3 gene mutations: two identified with deletion and one with duplication. All underwent an extensive clinical evaluation, including information collected from parents, Autism Diagnostic Interview Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) tests to diagnose or rule out ASD. Neurological and dysmorphology examinations and clinical genetics evaluations were performed too. Additionally, an intellectual and functional evaluations with Griffiths Mental Development Scales and Vineland-II, respectively was done.Results. The patient 1 have a terminal deletion of chromosome 22 (q13.31q13.33), encompassing 51 genes (include SHANK3 gene) and the patient 3 have an interstitial deletion, involving partially of the SHANK3 gene. Both patients were diagnosed with PMS associated to GDD or IDD. The patient 2 was diagnosed with ASD and he has a duplication in the end of the chromosome 22 (q13.33), involving three genes: SHANK3, ACR, RABL2B.Discussion and Conclusion. Our findings are broadly in line with those reported in previous studies. Moreover, our study showed that the SHANK3 haploinsufficiency due to interstitial deletion, only disrupting the SHANK3 gene, is enough to cause a set of features associated with PMS, namely neurobehavioral manifestations. Besides, this case highlights the hypothesis that perhaps not only the haploinsufficiency of SHANK3 is associated to ASD, but also the SHANK3 overexpression.

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Lee, Yi-Chung, and 李宜中. "Mutational spectrum of demyelinating Charcot-Marie-Tooth disease, genotype-phenotype correlation and functional study of MPZ mutations." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/95481993822496701561.

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博士 國立陽明大學 臨床醫學研究所 96 Charcot-Marie-Tooth disease (CMT) is a group of inherited neuropathies that can be further categorized according to their causative genes. CMT1B is a demyelinating neuropathy caused by mutations in the myelin protein zero gene (MPZ) on chromosome 1q22-q23. The site and nature of MPZ mutations are closely related to the corresponding clinical phenotypes. Although more than 110 different mutations in MPZ have been reported worldwide, few studies have been conducted in the Chinese population. This research focused on MPZ to ascertain its molecular epidemiology and spectrum of mutations among the Chinese in Taiwan. Furthermore, this work also examined the genotype-phenotype correlation and molecular pathophysiological mechanisms of MPZ by cell expression and functional assays. Mutational analyses performed in 99 unrelated patients with demyelinating CMT revealed a PMP22 duplication in 52.5% of patients, CX32 mutations in 8.1%, MPZ mutations in 7.1%, PMP22 mutations in 2%, and no changes in EGR2, LITAF, and NEFL genes. So far, seven MPZ mutations have been identified, including V58D, S63F, T65I, R98C, R98H, G123S, and S233fs. Among them, V58D and G123S are novel mutations. Genotype-phenotypes analyses have revealed a large variation between different MPZ mutations and corresponding phenotypes, which are independent of the accompanying clinical manifestations, neuropathological features, or nerve conduction velocities. Nevertheless, the median nerve motor conduction velocity (MNCV) has a tendency to be concordant with a particular MPZ mutation. However, median MNCV cannot be used to distinguish CMT1B with MPZ mutations from CMT1A with a PMP22 duplication. Twelve MPZ mutations linked to early onset CMT1 (V58D, S63F, T65I, R227S, and S233fs), late onset CMT1 (R98H and G123S), DSS (I30T and R98C), and axonal CMT (S44F, D75V, and T124M) were evaluated for their effects on the intracellular trafficking and cell adhesion function. Fluorescence analysis of CHO-K1 cells expressing wild type and mutant P0 fused with EGFP or monomeric DsRed demonstrated three different intracellular localization patterns. Wild type P0, P0 I30T, S44F, V58D, S63F, T65I, D75V, T124M, and R227S are all localized to the cell membrane. However, P0 R98H, R98C, and G123S mainly resided in the ER and Golgi apparatus. P0 S233fs formed aggregates within the ER. Adhesion assays demonstrated a variable decline in adhesiveness of cells expressing different mutant P0, as compared with cells expressing wild type P0. Furthermore, no significant correlation between the clinical phenotypes, cellular expression patterns, and adhesive properties of cells expressing different mutant P0 could be found. These studies suggest that the molecular pathological mechanism of P0 mutations are very complex and consist of at least two components consisting of defective transportation and impaired self-adhesion. This complexity may be attributed to the highly variable clinical manifestations of different P0 mutations.

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CUCINOTTA, Francesca. "ARRAY-CGH nei Disturbi di Spettro Autistico: ricaduta diagnostica e impatto sulla pratica clinica." Doctoral thesis, 2021. https://hdl.handle.net/11570/3221420.

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Autism Spectrum Disorder (ASD) is endowed with impressive heritability estimates and high recurrence rates; its genetic underpinnings are very heterogeneous and include many common and rare variants. Array-comparative genomic hybridization (CGH) offers significant sensitivity for the identification of copy number variations (CNVs) which can be a susceptibility factor for ASD. The aim of this study was to evaluated diagnostic yield and clinical impact of chromosomal microarray analysis in ASD. We performed Array-CGH for 329 ASD patients; four authors in accordance with the American College of Medical Genetics and Genomics recommendation blindly classified outcomes. After, patients were reassessed, further medical testing derived from the outcome of array-CGH was requested. Pathogenic/likely pathogenic CNV were identified in about 15.2% of patients and in about 27.1% were detected as possibly causal. Among patients with pathogenic/likely pathogenic CNV, in 52.0% the outcome of the array-CGH led to request other diagnostic tests that would not otherwise have been performed. From the results received to date, we have positive outcomes in the 55.0% of the exams. The results of our study highlighting the relevance of array-CGH in the genetic of diagnosis and underlie how its clinical translation can improve the care of children with ASD.

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Oliveira, Joao Miguel Goncalves de. "Autismo e Sindrome de Ehlers-Danlos tipo IV - comparação de fenótipo." Master's thesis, 2017. http://hdl.handle.net/10316/82344.

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Trabalho de Projeto do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina Anormalidades do tecido conjuntivo têm sido associadas a alterações da estrutura cerebral e a um vasto número de manifestações neuropsiquiatricas. Embora a literatura que relaciona Transtorno do Espectro Autista e Síndrome de Ehlers-Danlos tipo IV seja escassa, sugere que podem partilhar vias fisiopatologicas comuns. O presente estudo tem como objectivo comparar o fenótipo da Síndrome Ehler Danlos tipo IV com o fenótipo de autismo e determinar as características clinicas em comum. Para tal foi elaborada a pesquisa de artigos sobre TEA e EDS-HT com recurso ao motor de busca PubMed. Este estudo permitiu concluir que Transtornos do Espectro Autista e Síndrome de Ehlers-Danlos tipo IV partilham algumas características de fenotipo nomeadamente perturbações do equilíbrio, alterações da coordenação motora, dificuldades no controlo da postura, bem como alterações da neuroanatomia. O transtorno do espectro autista (TEA) é uma perturbação do neurodesenvolvimento complexa e multifactorial1 cujos sinais e sintomas costumam ser reconhecidos no segundo ano de vida (12 a 24 meses) e podem persistir com prejuízo clinicamente significativo no funcionamento social, profissional ou noutras áreas importantes da vida do indivíduo2. A observação de défices persistentes na comunicação e interação social em múltiplos contextos e a observação de padrões restritos e repetitivos de comportamento, interesses ou actividades constitui a base do diagnóstico de acordo com o manual diagnóstico e estatístico de transtornos mentais (DSM-V). O TEA tem sintomatologia extensa7, classificada em ligeira, moderada ou grave, sendo esta classificação baseada nos níveis exigidos de apoio necessários para auxiliar o doente. Connective tissue abnormalities have been associated with changes in brain structure and a large number of neuropsychiatric manifestations. Although the literature relating to Autism Spectrum Disorder and Ehlers-Danlos Syndrome type IV is scarce, it suggests that they may have common pathophysiological pathways. The present study aims to compare the phenotype of the Ehler Danlos Syndrome type IV with the autism phenotype and to determine the clinical characteristics in common. For that purpose, the research of articles on TEA and EDS-HT was made using the PubMed search engine. We concluded that Autism Spectrum Disorders and Ehlers-Danlos Syndrome type IV share some phenotype characteristics, in particular: motor coordination impairment, difficulties in posture control and balance, as well as neuroanatomy anomalies. Introduction: Although hypermobility Ehlers-Danlos Syndrome is a disease withpredominantly rheumatologic manifestations, recent studies describe a large number of extraarticularmanifestations and psychiatric symptoms, including difficulties in social interaction,isolation, and learning difficulties. The literature on a possible association of Autism andHypermobility Ehlers-Danlos Syndrome is scarce, however, it suggests that these diseasesmay have clinical features in common.Objective: Compare the phenotype of hypermobility Ehlers-Danlos Syndrome with theautism phenotype and investigate clinical features in common.Methods: Articles research on autism phenotype and hypermobility Ehers-Danlos syndromewas made using the PubMed database.Conclusion: The study concluded that autism and hypermobility Ehlers-Danlos syndromeshare some phenotype features such as disturbances of balance, changes in motorcoordination, difficulties in controlling posture, higher prevalence of gastrointestinalsymptoms, depression and anxiety as well as some neuroanatomy anomalies.Keywords:Autism; autism spectrum disorder; joint hypermobility; ligament laxity; connective tissue;Ehlers Danlos syndrome; phenotype

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Jósewicz, Marta. "Temperamentalne i osobowościowe korelaty autystycznej charakterystyki zachowania." Doctoral thesis, 2017. https://depotuw.ceon.pl/handle/item/2351.

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Cechy autystyczne to zestaw specyficznych charakterystyk społecznych, komunikacyjnych i poznawczych, występujących zarówno u osób z zaburzeniami ze spektrum autyzmu (autism spectrum disorders, ASD), jak i – w mniejszym nasileniu oraz liczbie – u osób z populacji ogólnej, w tym zwłaszcza u najbliższych krewnych osób z ASD. Zgodnie z teoretycznym modelem S. Barona-Cohena cechy te związane są z występowaniem ewolucyjnie ukształtowanej, wrodzonej odmienności neurobiologicznej, warunkującej nietypowe wzorce zachowań. Badanie tych cech jako jednego z elementów szerszego fenotypu autyzmu stanowi dynamicznie rozwijający się kierunek badań, w ramach którego eksploruje się m.in. powiązania między tymi cechami a innymi charakterystykami psychologicznymi. Celem badania było znalezienie odpowiedzi na pytanie o związek między cechami autystycznymi a temperamentem i osobowością. Ponadto dążono do uzyskania odpowiedzi na pytanie o różnice w zakresie nasilenia cech autystycznych pomiędzy studentami nauk ścisłych oraz nauk społecznych i humanistycznych (N = 208), a także pomiędzy rodzicami dzieci z autyzmem, rodzicami dzieci z zespołem Downa oraz rodzicami dzieci rozwijających się typowo (N = 178). Wykorzystano Kwestionariusz Autystycznej Charakterystyki Zachowania (AQ), kwestionariusz FCZ-KT oraz kwestionariusz NEO-PI-R. Wysokie nasilenie cech autystycznych powiązane było z niską żwawością, wytrzymałością, aktywnością i wrażliwością sensoryczną oraz wysoką reaktywnością emocjonalną. Analiza regresji wykazała, że cechy temperamentalne wyjaśniały 43% zmienności w zakresie cech autystycznych w grupie studentów oraz 7% zmienności tych cech w grupie rodziców. Najlepszymi predyktorami cech autystycznych była aktywność (w grupie studentów) i wrażliwość sensoryczna (u studentów i rodziców). Cechy autystyczne korelowały dodatnio z neurotyzmem oraz ujemnie z ekstrawersją, otwartością na doświadczenie i ugodowością. Przeprowadzona analiza skupień pokazała, że osoby o małej liczbie cech autystycznych są jednocześnie żwawe, aktywne i wytrzymałe, przejawiają niską reaktywność emocjonalną oraz są ekstrawertyczne, otwarte na doświadczenie, ugodowe i charakteryzują się niskim poziomem neurotyzmu. Osoby o wielu cechach autystycznych charakteryzują się niską żwawością, aktywnością i wytrzymałością, niską stabilnością emocjonalną oraz niską ekstrawertycznością i otwartością na doświadczenie. Analizy czynnikowe, w których uwzględniono cechy temperamentu i cechy autystyczne oraz cechy osobowości i cechy autystyczne, wskazały na częściową niezależność analizowanych konstruktów. Ponadto wykazano wyższe nasilenie cech autystycznych u studentów nauk ścisłych w porównaniu ze studentami nauk społecznych i humanistycznych. Rodzice dzieci z autyzmem nie różnili się pod względem opisywanej charakterystyki od rodziców dzieci z zespołem Downa i rodziców dzieci rozwijających się typowo. Autistic traits comprise of specific social, communicative and cognitive characteristics occurring both in people with autism spectrum disorder (ASD) and - with less intensity and in a smaller quantity - in general population, especially in relatives of those with ASD. According to the theoretical model of S. Baron-Cohen, these characteristics are related to the occurrence of an evolutionary, innate neurobiological variation, which determines unusual behavioural patterns. Examining these traits as one of the elements of broad autism phenotype (BAP) is a dynamically developing research direction, exploring, among others, the relationship between these characteristics and other psychological features.The primary purpose of the study conducted herein was to describe the relationship between autistic traits and temperament and personality traits. The secondary goal was to find an answer to the question concerning the differences in the intensity of autistic traits between sciences students on the one hand and humanities and social sciences students on the other (N = 208), as well as among parents of children with autism, parents of children with Down’s syndrome and parents of normally developing children (N = 178). The tools used were the Autism-Spectrum Quotient questionnaire (AQ), the Formal Characteristics of Behaviour – Temperament Inventory FCZ-KT and the NEO-PI-R. A high intensity of autistic traits was connected to low levels of briskness, endurance, activity and sensory sensitivity as well as a high degree of emotional reactivity. The regression analysis showed that the temperamental characteristics explained 43% of the variation in the autistic traits in the student group and 7% of the variability of these features in the parent group. The best predictors of autistic traits were activity (in student group) and sensory sensitivity (in students and parents). Autistic traits correlated positively with neuroticism and negatively with extroversion, openness to new experiences and agreeableness in the group of student and parent respondents. The clustered analysis showed that individuals with a low number of autistic features are both brisk, active and enduring, have low emotional reactivity, are extroverted, open to experience, agreeable, and have a low level of neurotism. People with many autistic features are characterized by low briskness, activity and endurance, low emotional stability and low extroversion and openness to experience. Factor analysis which included the characteristics of temperament and autistic features, personality traits and autistic features, indicated a partial independence of analyzed constructs. The results have also shown a higher degree of autistic traits in sciences students compared to humanities or social studies students. By contrast, parents of autistic children did not differ as regards the aforementioned traits from parents of children with Down’s syndrome or parents of normally developing children.

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Dissertations / Theses on the topic 'Phenotypic Spectrum'

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