title: Detection of copy-number variation in AUTS2 gene by targeted exonic array CGH in patients with developmental delay and autistic spectrum disorders.
abstract: Small genomic rearrangements and copy-number variations (CNVs) involving a single gene have been associated recently with many neurocognitive phenotypes, including intellectual disability (ID), behavioral abnormalities, and autistic spectrum disorders (ASDs). Such small CNVs in the Autism susceptibility candidate 2 (AUTS2) gene have been shown to be associated with seizures, ID, and ASDs. We report four patients with small CNVs ranging in size between 133-319 kb that disrupt AUTS2. Two patients have duplications involving single exons, whereas two have deletions that removed multiple exons. All patients had developmental delay, whereas two patients had a diagnosis of ASDs. The CNVs were detected by an exon-targeted array CGH with dense oligonucleotide coverage in exons of genes known or hypothesized to be causative of multiple human phenotypes. Our report further shows that disruption of AUTS2 results in a variety of neurobehavioral phenotypes. More importantly, it demonstrates the utility of targeted exon array as a highly sensitive clinical diagnostic tool for the detection of small genomic rearrangements in the clinically relevant regions of the human genome.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Sandesh C S
authors.initials: SC
authors.lastname: Nagamani
authors.forename: Ayelet
authors.initials: A
authors.lastname: Erez
authors.forename: Bruria
authors.initials: B
authors.lastname: Ben-Zeev
authors.forename: Moshe
authors.initials: M
authors.lastname: Frydman
authors.forename: Susan
authors.initials: S
authors.lastname: Winter
authors.forename: Robert
authors.initials: R
authors.lastname: Zeller
authors.forename: Dima
authors.initials: D
authors.lastname: El-Khechen
authors.forename: Luis
authors.initials: L
authors.lastname: Escobar
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
mesh_terms: D000293:Adolescent; D002659:Child Development Disorders, Pervasive / Q000209:etiology / Q000235:genetics*; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization / Q000379:methods; D003598:Cytoskeletal Proteins; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000209:etiology / Q000235:genetics*; D005091:Exons; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D011506:Proteins / Q000235:genetics*; D014157:Transcription Factors
chemical_list: C554283:AUTS2 protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins; D014157:Transcription Factors