Academic literature on the topic 'Monosomy 1p36'

Monosomy 1p36 is considered the most common subtelomeric deletion syndrome in humans and it accounts for 0.5–0.7% of all the cases of idiopathic intellectual disability. The molecular diagnosis is often made by microarray-based comparative genomic hybridization (aCGH), which has the drawback of being a high-cost technique. However, patients with classic monosomy 1p36 share some typical clinical characteristics that, together with its common prevalence, justify the development of a less expensive, targeted diagnostic method. In this study, we developed a simple, rapid, and inexpensive real-time quantitative PCR (qPCR) assay for targeted diagnosis of monosomy 1p36, easily accessible for low-budget laboratories in developing countries. For this, we have chosen two target genes which are deleted in the majority of patients with monosomy 1p36:PRKCZandSKI. In total, 39 patients previously diagnosed with monosomy 1p36 by aCGH, fluorescentin situhybridization (FISH), and/or multiplex ligation-dependent probe amplification (MLPA) all tested positive on our qPCR assay. By simultaneously using these two genes we have been able to detect 1p36 deletions with 100% sensitivity and 100% specificity. We conclude that qPCR ofPRKCZandSKIis a fast and accurate diagnostic test for monosomy 1p36, costing less than 10 US dollars in reagent costs.

Monosomy 1p36 syndrome is one of the most common submicroscopic deletion syndromes, which is characterized by the presence of delayed developmental milestones, intellectual disability, and clinically recognizable dysmorphic craniofacial features. The syndrome comprises 4 cytogenetic groups including pure terminal deletions, interstitial deletions, complex rearrangements, and derivative chromosomes 1 due to unbalanced translocations, where unbalanced translocations represent the least percentage of all cases of monosomy 1p36 (7%). Most patients with monosomy 1p36 due to an unbalanced translocation can be cytogenetically diagnosed using conventional techniques. However, chromosomal microarray analysis is mandatory in these cases to detect copy number variance and size of the deletion and allows for setting a phenotype-genotype correlation. Here, we studied a 1.5-year-old female patient who showed intellectual disability, delayed milestones, hypotonia, seizures, and characteristic dysmorphic features including brachycephaly, straight eyebrows, deep-set eyes, downslanting palpebral fissures, midface hypoplasia, depressed nasal bridge, long philtrum, and pointed chin. Conventional cytogenetic analysis (CCA), microarray study, and fluorescence in situ hybridization (FISH) analysis were performed. CCA showed a translocation involving chromosomes 1 and 21, 45,XX,der(1)t(1;21)(p36.32;q21.1)dn. Microarray analysis revealed copy number losses at both 1p36 and proximal 21q. FISH confirmed the presence of the 1p36 deletion, but was not performed for 21q. We have concluded that phenotype-genotype correlation for monosomy 1p36 syndrome can be performed for the fundamental clinical manifestations; however, the final aspect of the syndrome depends on composite factors. Monosomy 1p36 due to unbalanced translocation may present either classically or with additional altered features of various severity based on the copy number variations involving different chromosomes.

There is a substantial body of research indicating that compromised social functioning for individual with intellectual disabilities can have far reaching implications for quality of life, community participation and well being. As the implications of such findings are so important for people with intellectual disabilities the research has grown at a fast pace. However, an inherent difficulty for research on social functioning is the lack of definitions for key concepts in the area. The current paper reviews the available definitions for four concepts related to sociability (social cognition, social competence, social skills and social behaviour) a concept which itself is poorly defined. By reviewing the definitions available in the wider social and cognitive psychology literature and comparing these to definitions provided in research with individuals with learning disabilities it is clear that some of the concepts are poorly defined. The current article suggests possible working definitions which may be used as the impetus for future debate in the area. The clinical implications of having implicitly understood concepts rather than definable and measurable traits are considered. The review calls for researchers to provide definitions for the concepts being investigated and to consider the measures employed

Rearranjos subteloméricos submicroscópicos são uma causa importante de malformações congênitas múltiplas e retardo mental. Recentemente, os mecanismos de origem de rearranjos subteloméricos começaram a ser investigados. O seqüenciamento dos pontos de quebra de rearranjos cromossômicos em 1p36 revelou predomínio por mecanismos de reparo não exclusivos. Rearranjos constitucionais em 1p36 são as alterações subteloméricas mais comuns e incluem deleções terminais simples, cromossomos derivados, deleções intersticiais e rearranjos complexos. Estes rearranjos resultam em um padrão específico de malformações e distúrbios do desenvolvimento neuropsicomotor que caracterizam a síndrome de monossomia 1p36. Os genes causativos ainda não foram identificados e a expressão fenotípica pode ser em função da haploinsuficiência de genes contíguos ou pelo mecanismo de efeito de posição. Obesidade e hiperfagia são características descritas em ~15% dos casos. Investigamos por MLPA (Multiplex ligation-dependent probe amplification) a presença de rearranjos no segmento cromossômico 1p36 em um grupo de 154 pacientes com obesidade e hiperfagia e testes genéticos negativos para a síndrome de Prader-Willi (PWS), e outro grupo de 83 pacientes encaminhados para estudos cromossômicos por diversos motivos. A estratégia de MLPA utilizada permitiu identificar em nove pacientes diferentes tipos de rearranjos na região subtelomérica 1p36. Para investigar os mecanismos de quebra, reparo e estabilização cromossômica envolvidos em rearranjos subteloméricos, linhagens celulares de seis pacientes contendo rearranjos constitucionais em 1p36 foram desenvolvidas. A clonagem e seqüenciamento das junções dos pontos de quebra de um rearranjo complexo e três translocações não recíprocas identificaram similaridades nas junções que sugerem o reparo por NHEJ (Nonhomologous end-joining) como o mais provável mecanismo de origem destes rearranjos. Duas deleções terminais aparentemente simples também foram investigadas e o refinamento dos pontos de quebra identificou dois intervalos genômicos distintos contendo duplicações segmentares específicas de 1p36 com 90-98% de homologia. Estas duplicações segmentares podem ter estimulado ou sido usadas como substratos no mecanismo de reparo do DNA. Nossos achados reforçam a associação da monossomia 1p36 com obesidade e hiperfagia e sugerem que estas características estejam freqüentemente associadas com fenótipos atípicos/leves e deleções submicroscópicas com 2-3 Mb de extensão. Sugerimos o uso de MLPA como um método alternativo rápido de diagnóstico para detectar e caracterizar rearranjos em 1p36.
Subtelomeric abnormalities are an important cause of mental retardation and birth defects. The mechanisms involved in the formation of subtelomeric rearrangements are now beginning to be elucidated. Breakpoint sequencing analysis of 1p36 rearrangements has revealed prevalence of different nonexclusive recombination-repair mechanisms. Rearrangements of 1p36 are the most frequently detected subtelomeric abnormalities and include different-sized simple terminal deletions, derivative chromosomes, interstitial deletions and complex rearrangements. These rearrangements have been reported to result in the specific pattern of malformation and neurodevelopmental disabilities that characterizes monosomy 1p36 syndrome. Thus far, no genes have been conclusively determined to be causative. Besides, it is still not known if a mechanism of haploinsufficiency or position effect that influences phenotype expression in this commonest terminal deletion syndrome. Obesity and hyperphagia have been reported to occur in ~15% of cases. We have used multiplex ligation-dependent probe amplification (MLPA) to screen for monosomy 1p36 in a group of 154 hyperphagic and obese, PWS negative patients and in a separate group of 83 patients sent to investigate a variety of other conditions. The MLPA strategy used allowed the identification of a diversity of rearrangements in nine subjects. In order to gain further insights into the mechanisms of chromosome breakage, repair, and stabilization mediating subtelomeric rearrangements in humans, we have used cell lines containing constitutional rearrangements of 1p36 of six patients. Cloning of the breakpoint junctions in a complex rearrangement and three non-reciprocal translocations revealed similarities at the junctions that suggest NHEJ as the most likely mechanism of DNA repair that generated these rearrangements. Additionally, two apparently pure terminal deletions were also investigated and the refinement of the breakpoint regions identified two distinct genomic intervals ~25-kb apart, each containing a series of 1p36 specific segmental duplications with 90-98% identity. These segmental duplications might have been stimulated or used as substrate for a recombination-repair mechanism. Our work reinforces the association between monosomy 1p36 and obesity and hyperphagia, and further suggests that these features might be usually associated with an atypical/mild phenotype in addition to a submicroscopic deletion of ~2 to 3 Mb in size. We suggest the use of MLPA as an alternative method for high-throughput detection and delineation of rearrangements at 1p36.

This thesis comprises a qualitative meta-synthesis of research into parents' experiences of raising a child with a disability and a qualitative investigation into mothers' experiences of receiving a diagnosis of Monosomy 1p36 Deletion Syndrome for their child. A meta-synthesis of six papers meeting inclusion and quality criteria is presented within this review. Overarching themes derived from the papers included two risk factors: Experiences and Challenges; and two protective factors: Strategies for Coping and Support. These are presented in a visual representation of a parent's journey of raising a child with a disability. Using Grounded Theory techniques data were collected through semi-structured interviews with eight mothers who had received a diagnosis of Monosomy 1p36 Deletion Syndrome. An overarching theme of facing uncertainty/reducing uncertainty emerged from the data, and this was connected with five themes: gaining information, being supported/not being supported, being powerless, jumping to the future/living in the here-and-now, and diagnosis making a difference / diagnosis not making a difference. These findings highlight the need for professionals to be appropriately skilled to deliever a diagnosis whilst drawing on previous findings of research into delivering a diagnosis of Down's Syndrome, cancer and Dementia.