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.
- 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
- genotype-phenotype correlation
- chromosome microdeletion
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