Detection of small copy number variations (CNVs) in autism spectrum disorder (ASD) by custom array comparative genomic hybridization (aCGH)

Abstract Autism spectrum disorder (ASD) has a strong genetic basis and advances in genomic scanning methods have resulted in the identification of the underlying alterations in about 30% of the cases. The overwhelming majority of these alterations are either sequencing variants or large copy number variations (CNVs). In this pilot study, we tested whether the use of a customized array comparative genomic hybridization (aCGH), targeting exons of 269 ASD candidate genes, would allow the identification of small potentially pathogenic CNVs ( MBD2 and SLC17A6 , were smaller than 100 Kb. In a subsequent screening of other 407 patients and 350 non-affected controls for CNVs involving SLC17A6 , a gene without previous documentation in the literature of involvement with neurodevelopmental disorders, we found intragenic duplications in another proband but also in five controls. Of note, a commercial 500 K SNP-array did not detect the smallest gains in SLC17A6 . Our results suggest that small CNVs contribute to the etiology of ASD and that customized CGH array has significant potential to improve the sensitivity for detecting this class of alterations.