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Novel copy number variants in children with autism and additional developmental anomalies
Journal article   Open access   Peer reviewed

Novel copy number variants in children with autism and additional developmental anomalies

L. K Davis, K. J Meyer, D. S Rudd, A. L Librant, E. A Epping, V. C Sheffield and T. H Wassink
Journal of neurodevelopmental disorders, Vol.1(4), pp.292-301
12/2009
DOI: 10.1007/s11689-009-9013-z
PMCID: PMC3164008
PMID: 21547721
url
https://doi.org/10.1007/s11689-009-9013-zView
Published (Version of record) Open Access

Abstract

Autism is a neurodevelopmental disorder characterized by three core symptom domains: ritualistic-repetitive behaviors, impaired social interaction, and impaired communication and language development. Recent studies have highlighted etiologically relevant recurrent copy number changes in autism, such as 16p11.2 deletions and duplications, as well as a significant role for unique, novel variants. We used Affymetrix 250K GeneChip Microarray technology (either Nsp I or Sty I) to detect microdeletions and duplications in a subset of children from the Autism Genetic Resource Exchange (AGRE). In order to enrich our sample for potentially pathogenic CNVs we selected children with autism who had additional features suggestive of chromosomal loss associated with developmental disturbance (positive criteria filter) but who had normal cytogenetic testing (negative criteria filter). We identified families with the following features: at least one child with autism who also had facial dysmorphology, limb or digit abnormalities, or ocular abnormalities. To detect changes in copy number we used a publicly available program, Copy Number Analyser for GeneChip® (CNAG) Ver. 2.0. We identified novel deletions and duplications on chromosomes 1q24.2, 3p26.2, 4q34.2, and 6q24.3. Several of these deletions and duplications include new and interesting candidate genes for autism such as syntaxin binding protein 5 ( STXBP5 also known as tomosyn ) and leucine rich repeat neuronal 1 ( LRRN1 also known as NLRR1 ). Lastly, our data suggest that rare and potentially pathogenic microdeletions and duplications may have a substantially higher prevalence in children with autism and additional developmental anomalies than in children with autism alone.
Chromosome 1q24 Autism Copy number variation Dysmorphology Chromosome 4q34.2 Structural variation Chromosome 3p26.3 Chromosome 6q24 STXBP5 LRRN1 Chromosome 22q11.2 Mental retardation

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