Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype-phenotype correlations. Issue 6 (23rd September 2005)

• Record Type: Journal Article
• Authors: Sahoo, T; Peters, S U; Madduri, N S; Glaze, D G; German, J R; Bird, L M; Barbieri-Welge, R; Bichell, T J; Beaudet, A L; Bacino, C A
• Is Part Of: Journal of medical genetics. Volume 43:Issue 6(2006)
• Page Start: 512
• Page End: 516
• Publication Date: 2005-09-23
• Subjects: ADI-R, Autism Diagnostic Interview, revised -- ADOS-G, Autism Diagnostic Observation Schedule, Generic -- AED, antiepileptic drug -- AS, Angelman Syndrome -- BAC, bacterial artificial chromosome -- BSID-II, Bayley Scale of Infant Development, second edition -- CGH, comparative genomic hybridization -- FISH, fluorescent in situ hybridisation -- FMRP, fragile X mental retardation protein -- FOC, fronto-occipital circumference -- PLS-III, Preschool Language Scale, third edition -- PWS, Prader-Willi Syndrome -- SNRPN, small nuclear ribonucleoprotein polypeptide-N -- UBE3A, E6 associated protein ubiquitin protein ligase 3A gene -- VABS, Vineland Adaptive Behavior Scale; Angelman Syndrome -- comparative genomic hybridization -- autism -- genotype-phenotype correlation -- chromosome microdeletion; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2005.036913
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: Angelman syndrome (AS) is a neurodevelopmental disorder characterised by severe mental retardation, dysmorphic features, ataxia, seizures, and typical behavioural characteristics, including a happy sociable disposition. AS is caused by maternal deficiency of UBE3A (E6 associated protein ubiquitin protein ligase 3A gene), located in an imprinted region on chromosome 15q11-q13. Although there are four different molecular types of AS, deletions of the 15q11-q13 region account for approximately 70% of the AS patients. These deletions are usually detected by fluorescence in situ hybridisation studies. The deletions can also be subclassified based on their size into class I and class II, with the former being larger and encompassing the latter. Methods: We studied 22 patients with AS due to microdeletions using a microarray based comparative genomic hybridisation (array CGH) assay to define the deletions and analysed their phenotypic severity, especially expression of the autism phenotype, in order to establish clinical correlations. Results: Overall, children with larger, class I deletions were significantly more likely to meet criteria for autism, had lower cognitive scores, and lower expressive language scores compared with children with smaller, class II deletions. Children with class I deletions also required more medications to control their seizures than did those in the class II group. Conclusions: There are four known genes ( NIPA1, NIPA2, CYFIP1, & GCP5 ) that are affected by class I but not class II deletions, thus raising the possibility of a role for these genes in autism as well as the development of expressive language skills.