Disruption of contactin 4 in three subjects with autism spectrum disorder

• Published in: Journal of medical genetics Vol. 46; no. 3; pp. 176 - 182
• Main Authors: Roohi, J, Montagna, C, Tegay, D H, Palmer, L E, DeVincent, C, Pomeroy, J C, Christian, S L, Nowak, N, Hatchwell, E
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.03.2009; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Adolescent; Alu Elements; Artificial chromosomes; Autism; Autistic Disorder - genetics; Autistic Disorder - pathology; Biological and medical sciences; Cell Adhesion Molecules, Neuronal - genetics; Child; Child clinical studies; Chromosomes, Human, Pair 3; Cloning; Comparative Genomic Hybridization; Contactins; Developmental disabilities; Developmental disorders; Families & family life; Female; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene Dosage; Gene Duplication; Genetics of eukaryotes. Biological and molecular evolution; Genomes; Humans; In Situ Hybridization, Fluorescence; Infant; Infantile autism; Laboratories; Letters to JMG; Male; Medical genetics; Medical sciences; Molecular and cellular biology; Mutation; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Twins; Young Adult; United States > US; Human; Autism; Genetics; Pervasive developmental disorder; Developmental disorder; Disruption
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2008.057505

Background:Autism spectrum disorder (ASD) is a developmental disorder of the central nervous system of largely unknown aetiology. The prevalence of the syndrome underscores the need for biological markers and a clearer understanding of pathogenesis. For these reasons, a genetic study of idiopathic ASD was undertaken.Methods and results:Array based comparative genomic hybridisation identified a paternally inherited chromosome 3 copy number variation (CNV) in three subjects: a deletion in two siblings and a duplication in a third, unrelated individual. These variations were fluorescence in situ hybridisation (FISH) validated and the end points further delineated using a custom fine tiling oligonucleotide array. Polymerase chain reaction (PCR) products unique to the rearrangements were amplified and sequence analysis revealed the variations to have resulted from Alu Y mediated unequal recombinations interrupting contactin 4 (CNTN4).Conclusion:CNTN4 plays an essential role in the formation, maintenance, and plasticity of neuronal networks. Disruption of this gene is known to cause developmental delay and mental retardation. This report suggests that mutations affecting CNTN4 function may be relevant to ASD pathogenesis.