Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype-phenotype correlations

J Med Genet. 2006 Jun;43(6):512-6. doi: 10.1136/jmg.2005.036913. Epub 2005 Sep 23.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angelman Syndrome / diagnosis*
  • Angelman Syndrome / genetics
  • Autistic Disorder / diagnosis
  • Autistic Disorder / genetics
  • Base Sequence
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 15
  • Female
  • Genetic Testing / methods
  • Genotype
  • Humans
  • Infant
  • Male
  • Oligonucleotide Array Sequence Analysis / methods*
  • Phenotype
  • Seizures / diagnosis
  • Seizures / genetics
  • Sequence Deletion*