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Relevant bibliographies by topics / Novel Missense Mutation

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Academic literature on the topic 'Novel Missense Mutation'

Author: Grafiati

Published: 4 June 2021

Last updated: 6 September 2023

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Journal articles on the topic "Novel Missense Mutation"

1

Zhang, Edward D., Meixia Zhang, Gen Li, Charlotte L. Zhang, Zhihuan Li, Guangxi Zang, Zhiguang Su, et al. "Mutation spectrum in GNAQ and GNA11 in Chinese uveal melanoma." Precision Clinical Medicine 2, no. 4 (November 13, 2019): 213–20. http://dx.doi.org/10.1093/pcmedi/pbz021.

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Abstract Uveal melanoma is the most common intraocular cancer in the adult eye. R183 and Q209 were found to be mutational hotspots in exon 4 and exon 5 of GNAQ and GNA11 in Caucasians. However, only a few studies have reported somatic mutations in GNAQ or GNA11 in uveal melanoma in Chinese. We extracted somatic DNA from paraffin-embedded biopsies of 63 Chinese uveal melanoma samples and sequenced the entire coding regions of exons 4 and 5 in GNAQ and GNA11. The results showed that 33% of Chinese uveal melanoma samples carried Q209 mutations while none had R183 mutation in GNAQ or GNA11. In addition, seven novel missense somatic mutations in GNAQ (Y192C, F194L, P170S, D236N, L232F, V230A, and M227I) and four novel missense somatic mutations in GNA11 (R166C, I200T, S225F, and V206M) were found in our study. The high mutation frequency of Q209 and the novel missense mutations detected in this study suggest that GNAQ and GNA11 are common targets for somatic mutations in Chinese uveal melanoma.

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Nguyen, Thi Kim Lien, Van Dem Pham, Thu Huong Nguyen, Trung Kien Pham, Thi Quynh Huong Nguyen, and Huy Hoang Nguyen. "Three Novel Mutations in the NPHS1 Gene in Vietnamese Patients with Congenital Nephrotic Syndrome." Case Reports in Genetics 2017 (2017): 1–7. http://dx.doi.org/10.1155/2017/2357282.

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Congenital nephrotic syndrome, a rare and severe disease, is inherited as an autosomal recessive trait. The disease manifests shortly after birth and occurs predominantly in families of Finnish origin but has now been observed in all countries and races. Mutations in the NPHS1 gene, which encodes nephrin, are the main causes of congenital nephrotic syndrome in patients. In this study, we report the first mutational analysis of the NPHS1 gene in three unrelated children from three different Vietnamese families. These patients were examined and determined to be suffering from congenital nephrotic syndrome in the Department of Pediatrics, Vietnam National Hospital of Pediatrics. All 29 exons and exon-intron boundaries of NPHS1 were analyzed by PCR and DNA sequencing. Genetic analysis of the NPHS1 gene revealed one compound heterozygous variant p.Glu117Lys, one heterozygous missense mutation p.Asp310Asn, and one heterozygous frame-shifting mutation (c.3250_3251insG causing p.Val1084Glyfs⁎12) in patient 1. In patient 2, one heterozygous variant p.Glu117Lys and one novel heterozygous missense mutation p.Ser324Ala were identified. Finally, a novel missense mutation p.Arg802Leu and a novel nonsense mutation (c.2442C>G causing p.K792⁎) were identified in patient 3.

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Kapoor, Ritika R., Sarah E. Flanagan, Piers Fulton, Anupam Chakrapani, Bernadette Chadefaux, Tawfeg Ben-Omran, Indraneel Banerjee, Julian P. Shield, Sian Ellard, and Khalid Hussain. "Hyperinsulinism–hyperammonaemia syndrome: novel mutations in the GLUD1 gene and genotype–phenotype correlations." European Journal of Endocrinology 161, no. 5 (November 2009): 731–35. http://dx.doi.org/10.1530/eje-09-0615.

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BackgroundActivating mutations in the GLUD1 gene (which encodes for the intra-mitochondrial enzyme glutamate dehydrogenase, GDH) cause the hyperinsulinism–hyperammonaemia (HI/HA) syndrome. Patients present with HA and leucine-sensitive hypoglycaemia. GDH is regulated by another intra-mitochondrial enzyme sirtuin 4 (SIRT4). Sirt4 knockout mice demonstrate activation of GDH with increased amino acid-stimulated insulin secretion.ObjectivesTo study the genotype–phenotype correlations in patients with GLUD1 mutations. To report the phenotype and functional analysis of a novel mutation (P436L) in the GLUD1 gene associated with the absence of HA.Patients and methodsTwenty patients with HI from 16 families had mutational analysis of the GLUD1 gene in view of HA (n=19) or leucine sensitivity (n=1). Patients negative for a GLUD1 mutation had sequence analysis of the SIRT4 gene. Functional analysis of the novel P436L GLUD1 mutation was performed.ResultsHeterozygous missense mutations were detected in 15 patients with HI/HA, 2 of which are novel (N410D and D451V). In addition, a patient with a normal serum ammonia concentration (21 μmol/l) was heterozygous for a novel missense mutation P436L. Functional analysis of this mutation confirms that it is associated with a loss of GTP inhibition. Seizure disorder was common (43%) in our cohort of patients with a GLUD1 mutation. No mutations in the SIRT4 gene were identified.ConclusionPatients with HI due to mutations in the GLUD1 gene may have normal serum ammonia concentrations. Hence, GLUD1 mutational analysis may be indicated in patients with leucine sensitivity; even in the absence of HA. A high frequency of epilepsy (43%) was observed in our patients with GLUD1 mutations.

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Lee, Yejin, Hong Zhang, Figen Seymen, Youn Jung Kim, Yelda Kasimoglu, Mine Koruyucu, James P. Simmer, Jan C. C. Hu, and Jung-Wook Kim. "Novel KLK4 Mutations Cause Hypomaturation Amelogenesis Imperfecta." Journal of Personalized Medicine 12, no. 2 (January 24, 2022): 150. http://dx.doi.org/10.3390/jpm12020150.

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Amelogenesis imperfecta (AI) is a group of rare genetic diseases affecting the tooth enamel. AI is characterized by an inadequate quantity and/or quality of tooth enamel and can be divided into three major categories: hypoplastic, hypocalcified and hypomaturation types. Even though there are some overlapping phenotypes, hypomaturation AI enamel typically has a yellow to brown discoloration with a dull appearance but a normal thickness indicating a less mineralized enamel matrix. In this study, we recruited four Turkish families with hypomaturation AI and performed mutational analysis using whole exome sequencing. These analyses revealed two novel homozygous mutations in the KLK4 gene: a nonsense mutation in exon 3 (NM_004917.4:c.170C>A, p.(Ser57*)) was found in families 1, 2 and 3 and a missense mutation in exon 6 (c.637T>C, p.(Cys213Arg)) in family 4. Functional analysis showed that the missense mutation transcript could not translate the mutant protein efficiently or generated an unstable protein that lacked functional activity. The two novel inactivating KLK4 mutations we identified caused a hypomaturation AI phenotype similar to those caused by the four previously described KLK4 nonsense and frameshift mutations. This study improves our understanding of the normal and pathologic mechanisms of enamel formation.

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Song, Jian, Xuhui Zeng, Xiaoning Zhang, Yanwei Sha, and Xiuling Zhao. "Novel NLRP14 Mutations Induce Azoospermia." Andrologia 2023 (March 4, 2023): 1–9. http://dx.doi.org/10.1155/2023/9295049.

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Background. LR family pyrin domain-containing 14 (NLRP14 or NALP14) is one of the important members of the NLR family and was mainly expressed in testis. It is reported that deficiency in the NALP14 gene in mice can cause spermatogenic failure, and several NALP14 mutations have been found in oligospermia and infertile men. Case Presentation. This study reported two novel NALP14 mutations (c.2076delC: p.L697X and c.T2963C: p.F988S) in our patients with azoospermia. The exonic deletion mutation (c.2076delC) and one missense mutation (c.T2963C) were firstly screened out by whole-exome sequencing (WES) and further verified by amplifying and sequencing the specific exons 5 and 10. Histological analysis of testicular biopsy revealed that NALP14 expression was detected strongly in spermatogonia and weakly in early spermatocytes. Additionally, mutations in this gene caused meiotic arrest, and no postmeiotic round spermatids and mature spermatozoa were observed in the seminiferous tubules. Conclusions. This study and previous literatures showed that NLRP14 mutations are closely related to male infertility; we discovered two novel NALP14 mutations and summarized the kinds of literatures on NLRP14 mutations and male infertility. This is the first report that deletion mutation (c.2076delC) and one missense mutation (c.T2963C) in NALP14 all lead to azoospermia, which is still significant to the clinical auxiliary diagnosis of male infertility.

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Musumeci, Antonino, Francesco Calì, Carmela Scuderi, Mirella Vinci, Girolamo Aurelio Vitello, Sebastiano Antonino Musumeci, Valeria Chiavetta, et al. "Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy." Biomedicines 10, no. 9 (September 14, 2022): 2276. http://dx.doi.org/10.3390/biomedicines10092276.

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Recessive mutations in the POLR3A gene cause POLR3-HLD (the second-most-common form of childhood-onset hypomyelinating leukodystrophy), a neurodegenerative disorder featuring deficient cerebral myelin formation. To date, more than 140 POLR3A (NM_007055.3) missense mutations are related to the pathogenesis of POLR3-related leukodystrophy and spastic ataxia. Herein, in a cohort of five families from Sicily (Italy), we detected two cases of patients affected by POLR3-related leukodystrophy, one due to a compound heterozygous mutation in the POLR3A gene, including a previously undescribed missense mutation (c.328A > G (p.Lys110Glu)). Our study used an in-house NGS gene panel comprising 41 known leukodystrophy genes. Successively, we used a predictive test supporting the missense mutation as causative of disease, thus this mutation can be considered “Likely Pathogenic” and could be as a new pathogenetic mutation of the POLR3A gene causing a severe form of POLR3-HLD.

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Uyanik, G., N. Elcioglu, J. Penzien, C. Gross, Y. Yilmaz, A. Olmez, E. Demir, et al. "Novel truncating and missense mutations of the KCC3 gene associated with Andermann syndrome." Neurology 66, no. 7 (April 10, 2006): 1044–48. http://dx.doi.org/10.1212/01.wnl.0000204181.31175.8b.

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Background: Andermann syndrome (OMIM 218000) is an autosomal recessive motor-sensory neuropathy associated with developmental and neurodegenerative defects. The cerebral MRI reveals a variable degree of agenesis of the corpus callosum. Recently, truncating mutations of the KCC3 gene (also known as SLC12A6) have been associated with Andermann syndrome.Methods: The authors assessed clinically and genetically three isolated cases from Germany and Turkey with symptoms consistent with Andermann syndrome.Results: The authors detected four novel mutations within the KCC3 gene in their patients: two different truncating mutations in the first patient, a homozygous truncating mutation in the second, and a homozygous missense mutation in the third patient. In contrast to the classic phenotype of the Andermann syndrome linked to truncating KCC3 mutations the phenotype and the course of the disease linked to the missense mutation appeared to be different (i.e., showing additional features like diffuse and widespread white matter abnormalities).Conclusions: Not only truncating but also missense mutations of the KCC3 gene are associated with Andermann syndrome. Different types of KCC3 mutations may determine different clinical phenotypes.

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Gao, Shujuan, Min Lin, Yan Jin, Zhuona Wang, Yunqing Zhu, Guisheng Liu, and Xueyan Guo. "Three Novel Mutations of APC Gene Found in A Chinese Family with Familial Adenomatous Polyposis." Journal of Clinical and Nursing Research 6, no. 3 (May 30, 2022): 174–80. http://dx.doi.org/10.26689/jcnr.v6i3.3893.

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Objective: To identify the causative adenomatous polyposis coli (APC) gene defects associated with a pedigree of familial adenomatous polyposis (FAP). Methods: FAP was diagnosed based on clinical manifestations, family history, as well as endoscopic and pathological examinations. The blood samples of the FAP pedigree members, colonic polyp patients, and normal individuals were collected. Genomic DNA was then extracted from those samples. APC mutation analysis was conducted via direct polymerase chain reaction (PCR) sequencing. Results: Three synonymous mutations and a missense mutation were found: c.5034G>A (p.Gly1678Gly), c.5465T>A (p.Val1822Asp), c.5880G>A (p.Pro1960Pro), and c.5274T>G (p.Ser1758Ser). Among them, the homozygous mutation on APC gene c.5034G>A has been reported, while the other three mutations have not been reported in the Chinese Han population. Individuals with c.5465T>A (p.Val1822ASP) missense mutation eventually suffer from colon cancer and have poor prognosis. We found no mutation in patients with simple intestinal polyp and in normal individuals. In addition, there were homozygous and heterozygous mutations in different patients from the same family. Conclusion: Three new mutations of APC gene were firstly reported in Han population. The missense mutation of c.5465T>A (p.Val1822Asp) may be the cause of carcinogenesis in this FAP pedigree with poor prognosis.

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Fadiga, Lúcia, Mariana Lavrador, Nuno Vicente, Luísa Barros, Catarina I. Gonçalves, Asma Al-Naama, Luis R. Saraiva, and Manuel C. Lemos. "A Novel FGFR1 Missense Mutation in a Portuguese Family with Congenital Hypogonadotropic Hypogonadism." International Journal of Molecular Sciences 23, no. 8 (April 17, 2022): 4423. http://dx.doi.org/10.3390/ijms23084423.

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Congenital hypogonadotropic hypogonadism (CHH) is a rare reproductive endocrine disorder characterized by complete or partial failure of pubertal development and infertility due to deficiency of the gonadotropin-releasing hormone (GnRH). CHH has a significant clinical heterogeneity and can be caused by mutations in over 30 genes. The aim of this study was to investigate the genetic defect in two siblings with CHH. A woman with CHH associated with anosmia and her brother with normosmic CHH were investigated by whole exome sequencing. The genetic studies revealed a novel heterozygous missense mutation in the Fibroblast Growth Factor Receptor 1 (FGFR1) gene (NM_023110.3: c.242T>C, p.Ile81Thr) in the affected siblings and in their unaffected father. The mutation affected a conserved amino acid within the first Ig-like domain (D1) of the protein, was predicted to be pathogenic by structure and sequence-based prediction methods, and was absent in ethnically matched controls. These were consistent with a critical role for the identified missense mutation in the activity of the FGFR1 protein. In conclusion, our identification of a novel missense mutation of the FGFR1 gene associated with a variable expression and incomplete penetrance of CHH extends the known mutational spectrum of this gene and may contribute to the understanding of the pathogenesis of CHH.

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Park, Edward, Leiqian Tai, Peggy Nakagawa, Loan Hsieh, and Diane J. Nugent. "Novel Missense Mutations Associated with FXIII Deficiency and Bleeding." Blood 114, no. 22 (November 20, 2009): 4201. http://dx.doi.org/10.1182/blood.v114.22.4201.4201.

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Abstract Abstract 4201 Introduction Factor XIII deficient patients may present at any age, with a variety of bleeding symptoms, poor wound healing, and in females, frequent miscarriages. Factor XIII (FXIII) is a transglutaminase enzyme that was first discovered as a clotting protein in the coagulation cascade, but it is now understood that it cross-links proteins in the plasma, vascular matrix, endothelial cells, platelets and monocytes. In addition to maintaining normal hemostasis, FXIII plays a role in atherosclerosis, wound healing, inflammation, and pregnancy. FXIII circulates in plasma as a tetramer protein (FXIII-A2B2) held together by non-covalent bonds. FXIII has two catalytic A subunits (FXIII-A2) of 83kd and two non-catalytic B subunits or carrier subunits (FXIII-B2) of 79kd. Mutations have been identified in almost every exon of the FXIIIA subunit and often are unique to a particular cohort or family with Factor XIII deficiency. Our center has been characterizing patients with FXIII deficiency and has an IRB approved study to characterize bleeding phenotype in relation to genotype or mutational analysis. As part of this effort, we have identified 3 novel missense mutations, which we have not found in the FXIII database (<www.f13-database.de>) or in previous publications. Methods After obtaining informed consent, venous blood was collected in EDTA tubes for DNA isolation, PCR and ultimately DNA sequencing. DNA was isolated using QIAamp DNA Blood Midi Kit (Qiagen, Germantown, MD). Customary PCR was used to amplify the 15 exons for subunit A and the 12 exons for subunit B, using sequence specific primers based on previous publication and created to initiate outside of the encoding sequence. The nucleotide sequencing of amplified products was obtained via ABI 3730 DNA Analyzer (UCLA Sequencing and Genotyping Core). Results All three novel mutations were found in three, separate, unrelated individuals, with FXIII deficiency diagnosed early in life with a moderate to severe bleeding. Using the methods described above, the DNA sequencing and analysis for all exons for both the A and B subunits revealed three novel mutations, two on exon 12 subunit A and one on exon 10 subunit A. Patient 1 has a novel missense mutation in exon 10 at the 427 amino acid position, changing the aspartic acid into an asparagine (Asp427Asn) in the catalytic core. Patient 2 and 3 each had a unique mutation in exon 12. Exon 12 covers the transition from the catalytic core region and the Barrel 1 region of the FXIIIA molecule thus including portions of each functional region. Patient 2: An exon 12 missense mutation in aa 501 resulting in a change from glycine to an arginine (Gly501Arg) still in the catalytic core region. Patient 3 also had a mutation in exon 12 but in position 576 resulting in an amino acid change from threonine to methionine (Thr576Met) now in the Barrel 1 region. Patient 2 also had a missense mutation that has been previously reported in exon 3 (Arg77His) in the β-sandwich region. Three new missense mutations have been identified in patients with severe Factor XIII deficiency and a bleeding disorder. Previous reports of other point mutations in the FXIIIA catalytic core and barrel 1 regions have also been described in association with a hemorrhagic state in deficient patients. Ongoing protein expression studies will aid in our understanding of how these single amino acid substitutions result in such a serious bleeding diathesis. Disclosures: No relevant conflicts of interest to declare.

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Dissertations / Theses on the topic "Novel Missense Mutation"

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Kobayashi, Hiromasa. "A novel homozygous missense mutation of melanocortin-4 receptor (MC4R) in a Japanese woman with severe obesity." Kyoto University, 2004. http://hdl.handle.net/2433/148274.

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Yoshida, Hidetada. "Characterization of a novel missense mutation in the pore of HERG in a patient with long QTsyndrome." Kyoto University, 2001. http://hdl.handle.net/2433/150536.

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Saito, Hidehiko, Shigeru Shirakawa, Katsumi Deguchi, Hideo Wada, Eiichi Iwasaki, Junki Takamatsu, Isamu Sugiura, Tadashi Matsushita, and Koji Yamamoto. "Homozygous protein C deficiency: identification of a novel missense mutation that causes impaired secretion of the mutant protein C." Thesis, Elsevier, 1992. http://hdl.handle.net/2237/16344.

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Bidshahri, Arezoo (Roza). "Novel ultra-sensitive digital PCR assays for screening and detection of rare missense mutations in (proto)-oncogenes." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/62151.

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Somatic mutations can lead to cancer, often by altering the activity of kinases within signaling pathways that control cell growth and proliferation. Targeted cancer therapeutics are designed and used to regulate these aberrant signaling pathways in cases where somatic mutations within kinase genes predict a positive patient response to those treatments. For example, the V600E mutation in BRAF, the gene coding for the BRAF serine threonine kinase, predicts the effectiveness of vemurafenib in treating metastatic melanoma, while the mutational status of codons G12/G13 in the KRAS gene predicts likely colorectal cancer patient response to the monoclonal antibody (mAb) cetuximab.¹-³ However, FDA approved assays currently used to detect missense mutations in BRAF V600 and KRAS G12/G13 are not capable of detecting clinically actionable mutations at mutational frequencies low enough to permit their robust application to early disease detection or minimal residual disease monitoring. Moreover, detection of all clinically actionable missense mutations is not certain or generally achieved, in part due to limitations to assay specificities and the inability to unequivocally discriminate missense mutations from synonymous germline sequence variations. This thesis addresses that limitation through the development and validation of a novel platform for creating highly sensitive assays against all possible missense mutations in an oncogenic hotspot codon or adjacent set of hotspot codons that ameliorates the known limitations to current FDA-approved assays. The platform is designed to enable development of assays against all possible missense mutations in oncogenic hotspots and, if required, unequivocally differentiate them from synonymous germline alleles. It utilizes droplet digital PCR (ddPCR) technology and chimeric wild-type specific LNA/DNA probes to create a novel “WT-negative” screening paradigm. The platform is applied to the creation of two new assays of potential clinical use in cancer diagnostics and theranostics. The first provides a reliable and sensitive screening and detection of all known clinically actionable mutations in BRAF V600, and the second achieves the same for KRAS G12/G13. Both assays show complete diagnostic accuracy when applied to formalin-fixed paraffin-embedded (FFPE) tumor specimens from metastatic colorectal cancer patients deficient for Mut L homologue-1.
Applied Science, Faculty of
Graduate

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Gilardin, Laurent. "Identification des épitopes T d’ADAMTS13 chez les patients atteints de Purpura Thrombotique Thrombocytopénique The ADAMTS13¹²³⁹-¹²⁵³ peptide is a dominant HLA-DR1-restricted CD4⁺ T-cell epitope Purpura Thrombotique Thrombocytopénique : physiopathologie, clinique, pronostic et traitement In silico calculated affinity of FVIII-derived peptides for HLA class II alleles predicts inhibitor development in haemophilia A patients with missense mutations in the F8 gene In silico prediction of immuno-dominant T-cell epitopes on human therapeutic factor VIII Predictive immunogenicity of Refacto AF Complement C3 is a novel modulator of the anti-factor VIII immune response Anti-ADAMTS13 Autoantibodies against Cryptic Epitopes in Immune-Mediated Thrombotic Thrombocytopenic Purpura." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS520.

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Le purpura thrombotique thrombocytopénique (PTT) est une maladie autoimmune rare et grave caractérisée par la présence d’anticorps dirigés contre ADAMTS13 (A13), une protéase impliquée dans l’hémostase primaire. L’implication des lymphocytes T CD4⁺ spécifiques d’ADAMTS13, dans la physiopathologie de la maladie est suggérée par une restriction pour l’haplotype HLA-DRB1*11 (DR11), l’isotype IgG des anticorps. Dans ce travail, nous avons cherché à identifier les épitopes T d’A13. Tout d’abord, nous avons sélectionné in silico les peptides d’A13 susceptibles d’être présentés par les molécules HLA-DR11. Ensuite, l’étude de la liaison de ces peptides à des molécules HLA-DR11 par des tests ELISA compétitifs a permis d’identifier les peptides les plus affins. Enfin, nous avons déterminé les peptides d’ADAMTS13 reconnus par les lymphocytes T CD4⁺ de donneurs sains et de patients porteurs de l’haplotype DR11. Ces travaux ont également été reproduits pour l’haplotype HLA-DR1 et dans un modèle murin de souris transgéniques humanisées exprimant l’haplotype HLA-DR1. Les résultats de ce travail nous permettent d’envisager d’isoler des lymphocytes T CD4⁺ spécifiques d’ADAMTS13 chez les patients afin de mieux les caractériser aux différents stades de la maladie et de suivre leur évolution sous traitement dans le but de mieux anticiper les rechutes
Thrombotic thrombocytopenic purpura (TTP) is a rare and severe disease characterized by auto-antibodies directed against ADAMTS13 (A13), a plasmatic protein involved in haemostasis. The implication of CD4⁺ T cells in the pathogenesis of the disease is suggested by the existence of a restriction to particular HLA-DR alleles and by the IgG isotype of the antibodies. In this study, we wished to determine the T cell epitopes of A13. First, we selected in silico the immunodominant peptides, based on their binding capacity to HLA-DR11 molecules. Second, their binding capacity to purified HLA-DR11 molecules using a ELISA competitive assay led us to identify the best binder peptides. Finally, we determined the peptides recognized by human CD4⁺ T cells from DR11 healthy donors and patients. These results were reproduced for the HLA-DR1 haplotype and in a transgenic humanized HLA-DR1 mouse model. In a perspective point of view, our results will allow us to further isolate the specific CD4⁺ T cells in order to characterize them at different steps of the disease and during follow-up to better anticipate relapses

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Jorge, André Filipe Santos. "Molecular studies of a novel mutation in MYO7A gene in Usher Syndrome type I." Master's thesis, 2016. http://hdl.handle.net/10316/33413.

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Trabalho de revisão do 6º ano médico com vista à atribuição do grau de mestre (área científica de genética) no âmbito do ciclo de estudos de Mestrado Integrado em Medicina.
Introdução: O Síndrome de Usher (USH) é uma doença autossómica recessiva caracterizada por um quadro de défice auditivo neurosensorial e retinite pigmentar, associado ou não a disfunção vestibular. USH é dividido em três tipos, sendo o USH tipo I o mais grave, caraterizado por surdez grave a profunda bilateral congénita, disfunção vestibular e retinite pigmentar diagnosticada durante a infância. Nas famílias com USH tipo I, MYO7A é o gene mais frequentemente mutado (50%). Este gene codifica para a proteína Miosina VIIa, previamente descrita como uma proteína motor de transporte e participando na formação da adesão célula a célula. Num estudo anterior foi encontrada uma nova alteração (c.4489G>C) no gene MYO7A num doente português com USH tipo I. Este trabalho propôs-se a avaliar a possibilidade de esta alteração ser responsável pelo fenótipo. Métodos: Uma avaliação clínica completa foi feita de forma a confirmar o fenótipo do doente. As análises por Sequenciação do exão 34 do gene MYO7A da amostra do doente e por PCR-RFLP das amostras do doente e de 250 indivíduos normais sem USH foram efetuadas para avaliar a presença da alteração c.4489G>C. Adicionalmente, foram realizados estudos in silico, usando software disponíveis online e a conservação evolutiva num grupo de primatas e não primatas. Finalmente, para determinar a expressão da alteração c.4489G>C nos transcritos do gene MYO7A, foram estudadas amostras de epitélio nasal do doente e de dois indivíduos normais. Resultados/Discussão: Foi confirmada a presença da variante c.4489G>C no doente com USH do tipo I e a sua ausência em 250 indivíduos normais. Os softwares online usados demostraram que a variante era lesiva, provavelmente deletéria ou causadora da doença. O estudo da conservação evolutiva demonstrou uma região altamente conservada no genoma e na proteína, em todas as espécies estudadas. Foi ainda possível identificar a expressão da variante c.4489G>C nos transcritos da amostra do doente e a sua ausência nas amostras dos indivíduos normais. Conclusão: Assim, foi possível concluir que a nova alteração c.4489G>C do gene MYO7A é uma mutação missense homozigótica, provavelmente responsável pelo USH do tipo I no doente português e que a sua expressão foi encontrada nos transcritos do epitélio nasal do doente. Usher syndrome (USH) is an autosomal recessive disorder characterized by the association of a sensorineural hearing impairment and retinitis pigmentosa, with or without vestibular dysfunction. USH is divided in three types, being USH type I the most severe form, characterized by severe to profound congenital and bilateral sensorineural hearing loss, congenital vestibular dysfunction and retinitis pigmentosa diagnostic during childhood. In USH type I families, MYO7A is the most commonly mutated gene (50%). This gene codes for Myosin VIIa protein, previously described as a motor transport protein and participating in the establishment of cell-cell adhesions. In a previous study, it was found a novel homozygous variant (c.4489G>C) in MYO7A gene in an USH type I Portuguese patient. This work purposed to appraise the possibility of this variant be responsible for the phenotype. A complete evaluation was performed to ascertain the clinical phenotype of the patient. Patient’s sample Sequencing analysis of MYO7A gene exon 34 and PCR-RFLP analysis of patient and 250 DNA samples from normal individuals without USH was accomplished to assess the c.4489G>C variant presence. Additionally, in silico studies using available internet software and evolutionary conservation in a group of primates and non-primates was performed. Finally, in order to determine if the c.4489G>C variant allele was expressed in MYO7A gene transcripts, nasal epithelium samples from the patient and two normal individuals were studied. The presence of c.4489G>C variant in an USH type I patient and its absence in 250 normal individuals was confirmed. Internet software used determined that this variant was probably damaging, deleterious or disease causing. Evolutionary conservation study showed a highly conserved region both in nucleotide and amino acid sequences from Homo sapiens to Molecular studies of a novel mutation in MYO7A gene in Usher Syndrome type I 13 Caenorhabditis elegans. Expression of c.4489G>C variant in patient’s cDNA sample was identified as well as its absence in the two normal individuals cDNA samples. In conclusion, this study revealed that the novel c.4489G>C MYO7A gene variant is a homozygous missense mutation, probably responsible for USH type 1 in a Portuguese patient and its expression found in patient’s nasal epithelium transcripts.

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YAMADA, Takayuki, and 貴之山田. "A novel missense mutation causing abnormal LMAN1 in a Japanese patient with combined deficiency of factor V and factor VIII." Thesis, 2010. http://hdl.handle.net/2237/14437.

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Lakhotia, Smita. "Breast Cancer Susceptibility Gene 1 (BRCA1) And Breast Cancer." Thesis, 2006. http://hdl.handle.net/2005/456.

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Breast Cancer susceptibility gene 1 (BRCA1) & Breast Cancer Breast cancer is one of the most common malignancies affecting women worldwide. About 5-10% of all cases are estimated to be familial. Mutations in the BRCA1 (Breast Cancer susceptibility gene 1) gene account for about 15-20% of inherited breast cancer cases and 60-80% of families predisposed to both breast and ovarian cancer. BRCA1 mutations also result in susceptibility to early-onset breast and ovarian cancer. The human BRCA1 gene encodes a multi-domain 1,863 amino acid nuclear protein that is expressed in a wide variety of adult human tissues. The N-terminal end of BRCA1 contains a RING-finger domain. Exon 11 of BRCA1 contains two nuclear localization signals towards its N-terminal for targeting BRCA1 to the nucleus. The carboxyl terminus contains two BRCT (BRCA1 C-terminal) domains and a transcriptional activation domain. This study was carried out to functionally characterize BRCA1 and to find out the percentage in which BRCA1 gene is mutated in Indian familial breast and/or ovarian cancer families. The work has been divided into three sections: 1. Identification & characterization of a BRCA1 Associated Protein 2 (BAP2). 2. Germ-line BRCA1 mutation Analysis in Indian Breast and/or Ovarian Cancer Families. 3. Characterization of a novel missense mutation (E116K) in BRCA1. BRCA1 is known to interact with large number of proteins and is involved in various cellular functions like tumorigenesis, transcription, DNA damage repair, cell-cycle control, ubiquitinylation, genetic stability, cell growth and apoptosis. The interacting partners of BRCA1 have given a lot of clue about the functions of this complex protein. In the first project, we used the yeast two-hybrid system to identify novel interacting proteins of BRCA1. We used the 1-500 amino acid region of BRCA1 as bait in library screen and picked up a novel clone (clone 89) showing interaction with BRCA1. Clone 89 contains approximately 2.3 Kb long cDNA sequence. Using the nucleotide blast search, we obtained a full-length cDNA of approximately 5.4 Kb (KIAA0657) that is located on chromosome 2, 2q36.1 region. We have named this new protein BRCA1 Associated Protein 2 (BAP2). Translation of this coding sequence gave a protein that has homology to Titin protein. This protein, which has 1,236 amino acids, contains 9 Immunoglobulin like domains. The homologues of this protein exists in many other organisms but the function is not known. We have confirmed the interaction between BRCA1 and c89 using in vitro GST pull-down assay. We have studied the influence of BAP2 on various functions of BRCA1 like transcription, colony suppression and cell cycle. In the transcription assays, BAP2 activated p21 promoter activity perhaps by using endogenous BRCA1 as simultaneous ectopic expression of truncated BRCA1 (containing aa 1-500) abolished this activity. Further, BAP2 also increased the ability of BRCA1 to activate p21 promoter suggesting that BAP2 may act as a co-activator of BRCA1 functions. Surprisingly, we observed that BAP2 inhibited p53-mediated transcription both in the absence and presence of BRCA1. BAP2 failed to inhibit colony growth by itself as well as in combination with BRCA1. In the cell-cycle study, we found that BAP2 did not have any significant effect on cell cycle profile by itself. However, it drastically augmented the G2/M arrest mediated by BRCA1. Thus we conclude that we have identified a novel interacting protein of BRCA1 that regulates certain functions of BRCA1. Detection of mutations is of central importance in the study of genetic and malignant diseases. Mutation detection helps us in understanding the protein structure, function and expression. More than that, it is also important for pre-symptomatic/antenatal diagnosis, confirmation of the genetic cause of the disease and the mode of inheritance of a disease in a particular family, the prediction of clinical phenotype and the potentiation of diagnostic analysis in the case of families with incomplete pedigrees or with new mutations. Therefore, the importance of direct mutation analysis cannot be understated. The second project deals with screening of mutations in BRCA1 gene in 50 familial breast and/or ovarian cancer families using the technique of Conformation Sensitive Gel Electrophoresis (CSGE). CSGE can be used to detect mismatches in DNA heteroduplexes that contain one strand of wild type and one strand of mutated DNA. In a collaborative study with Kidwai Memorial Hospital for Oncology, Bangalore, we screened 50 families suffering from breast and/or ovarian cancer. We detected 13 mutations in this study out of which 3 are novel and 10 have already been reported earlier (Breast Information Core). All the mutations obtained in our study result in truncation of the BRCA1 protein either because of non-sense mutation or frame-shift mutation. Interestingly, 8 of the mutations detected are 185delAG mutations – the most commonly occurring mutation in Ashkenazi Jewish population. From this study, we conclude that BRCA1 is mutated in 26% of familial breast and/or ovarian cancer cases in India. Genetic testing in individuals with family history of breast, ovarian or both has become very common. It is difficult to interpret the result of genetic screen if a DNA change in the gene does not result in truncation of the protein. Rare missense changes of unknown functional and pathogenic significance are called unclassified variants. It is important to study the functional implications of these unclassified variants in order to determine the risk associated with the presence of such variations. The third project deals with characterization of one such missense variation. In an earlier mutation analysis study for BRCA1 gene in breast cancer samples, we found a novel missense variation resulting in Glu116Lys (E116K) change. In order to determine if this variant is a disease associated missense mutation or a benign sequence alteration; we introduced this variation into full length BRCA1 cDNA and studied its effect on the known functions of BRCA1, namely, transcription, colony suppression and cell cycle. We found that E116K is defective for activating transcription. However, it continued to inhibit growth in colony formation assay and arrest cells in G2/M phase of cell cycle. We conclude that E116K mutation results in loss of transactivation function of BRCA1 but has no effect on colony formation and cell cycle regulation; thus it can be categorized as a novel missense mutation.

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Book chapters on the topic "Novel Missense Mutation"

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Gardner, Jessica C., Tom R. Webb, Naheed Kanuga, Anthony G. Robson, Graham E. Holder, Andrew Stockman, Caterina Ripamonti, et al. "A Novel Missense Mutation in Both OPN1LW and OPN1MW Cone Opsin Genes Causes X-Linked Cone Dystrophy (XLCOD5)." In Retinal Degenerative Diseases, 595–601. Boston, MA: Springer US, 2011. http://dx.doi.org/10.1007/978-1-4614-0631-0_76.

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Spiegel, Ronen, Devorah Soiferman, Avraham Shaag, Stavit Shalev, Orly Elpeleg, and Ann Saada. "Novel Homozygous Missense Mutation in SPG20 Gene Results in Troyer Syndrome Associated with Mitochondrial Cytochrome c Oxidase Deficiency." In JIMD Reports, 55–60. Berlin, Heidelberg: Springer Berlin Heidelberg, 2016. http://dx.doi.org/10.1007/8904_2016_580.

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Castro-Ferreira, I., Rute Carmo, Sérgio Estrela Silva, Otília Corrêa, Susana Fernandes, Susana Sampaio, Rodrigues-Pereira Pedro, Augusta Praça, and João Paulo Oliveira. "Novel Missense LCAT Gene Mutation Associated with an Atypical Phenotype of Familial LCAT Deficiency in Two Portuguese Brothers." In JIMD Reports, 55–62. Berlin, Heidelberg: Springer Berlin Heidelberg, 2017. http://dx.doi.org/10.1007/8904_2017_57.

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Aalberts, J. J. J., A. G. Schuurman, G. Pals, B. J. C. Hamel, G. Bosman, Y. Hilhorst-Hofstee, D. Q. C. M. Barge-Schaapveld, B. J. M. Mulder, M. P. van den Berg, and J. P. van Tintelen. "Recurrent and founder mutations in the Netherlands: Extensive clinical variability in Marfan syndrome patients with a single novel recurrent fibrillin-1 missense mutation*." In De Nederlandse gezondheidszorg, 89–94. Houten: Bohn Stafleu van Loghum, 2014. http://dx.doi.org/10.1007/978-90-368-0705-0_12.

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Morita, Masashi, Shun Matsumoto, Airi Sato, Kengo Inoue, Dzmitry G. Kostsin, Kozue Yamazaki, Kosuke Kawaguchi, et al. "Stability of the ABCD1 Protein with a Missense Mutation: A Novel Approach to Finding Therapeutic Compounds for X-Linked Adrenoleukodystrophy." In JIMD Reports, 23–31. Berlin, Heidelberg: Springer Berlin Heidelberg, 2018. http://dx.doi.org/10.1007/8904_2018_118.

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Oldenburg, J., E. M. Quenzel, U. Harbrecht, A. Fregin, W. Kress, C. R. Müller, H. J. Hertfelder, R. Schwaab, H. H. Brackmann, and P. Hanfland. "Missense Mutations at ALA-10 in the Factor IX Propeptide: A Novel Mechanism for Severe Bleeding During Oral Anticoagulant Therapy." In 27. Hämophilie-Symposion Hamburg 1996, 285–92. Berlin, Heidelberg: Springer Berlin Heidelberg, 1998. http://dx.doi.org/10.1007/978-3-642-80403-8_43.

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Sheffer-Babila, S., VL Chin, TA Lee, and P. Zhou. "Unique Phenotypic Features Associated with a Novel Missense Mutation in the Ligand-Binding Domain of the Androgen Receptor Gene." In The Endocrine Society's 92nd Annual Meeting, June 19–22, 2010 - San Diego, P2–436—P2–436. Endocrine Society, 2010. http://dx.doi.org/10.1210/endo-meetings.2010.part2.p9.p2-436.

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Kawashima, Y., S. Okada, T. Botsubo, N. Miyahara, R. Nishimura, J. Nagaishi, K. Hanaki, and S. Kanzaki. "Mutated IGF-I Receptor (D1105E) Extinguish Autophosphorylation: A Family of Short Stature Born Intrauterine Growth Retardation Bearing a Novel Missense Mutation of the IGF-I Receptor." In The Endocrine Society's 92nd Annual Meeting, June 19–22, 2010 - San Diego, P1–662—P1–662. Endocrine Society, 2010. http://dx.doi.org/10.1210/endo-meetings.2010.part1.p14.p1-662.

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Derr, MA, P. Fang, SK Sinha, S. Ten, V. Hwa, and RG Rosenfeld. "A Novel Y332C Missense Mutation in the Intracellular Domain of the Human Growth Hormone Receptor (GHR) Does Not Alter STAT5b Signaling: Redundancy of GHR Intracellular Tyrosines Involved in STAT5b Signaling." In The Endocrine Society's 92nd Annual Meeting, June 19–22, 2010 - San Diego, P1–222—P1–222. Endocrine Society, 2010. http://dx.doi.org/10.1210/endo-meetings.2010.part1.p5.p1-222.

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Li, Wei. "Structural and Functional Consequences of the SMA-Linked Missense Mutations of the Survival Motor Neuron Protein: A Brief Update." In Novel Aspects on Motor Neuron Disease. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.81887.

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Conference papers on the topic "Novel Missense Mutation"

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Hisata, Shu, and Masahito Ebina. "A Novel Missense Mutation In Dyskeratosis Congenita With Pulmonary Disease." In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a5419.

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Cambraia, Amanda, Mario Campos Junior, Fernanda Gubert, Juliana Ferreira Vasques, Marli Pernes da Silva Loureiro, Claudio Heitor Gress, José Mauro Bráz de Lima, Rosalia Mendez Otero, and Verônica Marques Zembrzuski. "A novel mutation in the RRM2 domain of TDP-43 in a Brazilian sporadic ALS patient." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.486.

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Introduction: Amyotrophic Lateral Sclerosis (ALS) is an adult-onset progressive and fatal neurodegenerative disease that selectively affects upper and lower motor neurons. Death occurs within 3 to 5 years of onset, usually from respiratory complications. Most cases of ALS are sporadic (SALS), but familial forms of the disease (FALS) represent approximately 10% of the cases. More than 30 genes have been associated with ALS and mutations in these genes account for more than a half of all familial cases and about 10% of sporadic cases. One of the most prevalent genes is TARDBP, responsible for approximately 4-6% of FALS and nearly 1-2% of SALS cases. The aim of this study was to perform the screening of known ALS genes, to increase the knowledge of the mutations that circulate in the population from Rio de Janeiro. Methods: The screening of mutations was performed through the Illumina Next Generation Sequencing (NGS) platform with the use of a sequencing panel that contained the TARDBP, SOD1, FUS, VAPB, SMN1 and SMN2 genes. Results: A novel missense mutation (p.Phe194Leu) in exon 5 of the TARDBP gene was found in a sporadic male patient who died at the age of 58 (2018). The mutation, a TTT/CTT substitution, was not detected in any mutation databases and in the literature. In silico analysis of this variant with different algorithms were performed and the results pointed to a probably damaging impact and that the mutation is disease causing. Conclusion: Through the study of the ALS genes by the NGS, we were able to identify a novel TARDBP mutation in a non-familial ALS patient. In addition, this study also increases the number of known TARDBP mutations in ALS patients and our knowledge of the mutations that affect the patients from of population from Rio de Janeiro.

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Ivaskevicius, V., A. Biswas, B. Pezeshkpoor, B. Pötzsch, A. Pavlova, and J. Oldenburg. "A Novel Missense Mutation in ITGB3 Gene Causing Autosomal Dominant Glanzmann Thrombasthenia." In 63rd Annual Meeting of the Society of Thrombosis and Haemostasis Research. Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-1677716.

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Zavala, B., S. Akkineni, M. Mirsaeidi, and N. Nasiri. "Novel IL2RG Missense Mutation in a Patient with Recurrent Mycobacterium Avium Complex Infection." In American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7375.

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Ivaskevicius, Vytautas, Arijit Biswas, Martynas Vitkus, Sneha Singh, Anna Pavlova, and Johannes Oldenburg. "Impact of Novel Missense Mutation (p. Arg510Cys) in the FGA Gene Resulting in Dysfibrinogenemia." In Hamburger Hämophilie Symposion Hamburg, Germany. Georg Thieme Verlag KG, 2020. http://dx.doi.org/10.1055/s-0040-1721594.

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Brockmann, Knut, Renate Brackmann, Angela Abicht, Ingo Kurth, Jianying Huang, Stephen Waxman, and Sulayman Dib-Hajj. "Episodic Pain Syndrome Associated with a Novel Heterozygous Gain-of-Function SCN11A Missense Mutation." In Abstracts of the 45th Annual Meeting of the Society for Neuropediatrics. Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-1698164.

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Sansović, Ivona, Ljubica Odak, Adriana Bobinec, and Ingeborg Barišić. "97 A novel missense mutation inSGSHgene causing Sanfillipo type 3A mucopolysaccharidosis." In 10th Europaediatrics Congress, Zagreb, Croatia, 7–9 October 2021. BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health, 2021. http://dx.doi.org/10.1136/archdischild-2021-europaediatrics.97.

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Zuhlke, Kimberly A., Anna M. Johnson, Scott A. Tomlins, Nallasivam Palanisamy, Christiane M. Robbins, Waibhav A. Tembe, John D. Carpten, Ethan M. Lange, William B. Isaacs, and Kathleen A. Cooney. "Abstract 2564: Identification of a novel SPOP missense mutation from targeted next-generation sequencing of men with chromosome 17-q linkage." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-2564.

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Tiedt, Ralph, Elisa Degenkolbe, Pascal Furet, Brent A. Appleton, Joseph Schoepfer, David Ruddy, John Monahan, et al. "Abstract 4738: Cellular resistance screening with a novel selective c-Met inhibitor reveals a spectrum of missense mutations that partially overlap with activating mutations found in cancer patients." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-4738.

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