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Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype-phenotype correlations
  1. T Sahoo1,
  2. S U Peters1,
  3. N S Madduri1,
  4. D G Glaze1,2,
  5. J R German1,
  6. L M Bird3,4,
  7. R Barbieri-Welge3,
  8. T J Bichell3,
  9. A L Beaudet1,
  10. C A Bacino1
  1. 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
  2. 2Department of Neurology, Baylor College of Medicine, Houston, TX, USA
  3. 3San Diego Children’s Hospital, San Diego, CA, USA
  4. 4Department of Pediatrics, University of California, San Diego, CA, USA
  1. Correspondence to:
 Dr C A Bacino
 Associate Professor, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030; cbacino{at}bcm.tmc.edu

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.

  • 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

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Footnotes

  • Published Online First 23 September 2005

  • The first two authors contributed equally to this work.

  • Competing interests: there are no competing interests

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