A Genome Wide Copy Number Variations Analysis in Autism Spectrum Disorder (Asd) and Intellectual Disability (Id) in Italian Families

Abstract

Background: Autism Spectrum Disorders (ASD) and Intellectual Disability (ID) represent lifelong conditions with severe impact on behavior and lifestyle of patients and their families. Array comparative genomic hybridization (array-CGH) has clarified the underlying genetic causes of ASD and ID by CNVs identification in several chromosomal regions with susceptibility to different levels of severity of ASD or ID in up to 1% of patients. Methods: Using oligo array-CGH we analyzed 476 unrelated subjects with ASD or ID, thoroughly investigated by both child neuropsychiatrists and clinical geneticists. The inheritance of the CNV were tested in the majority of cases (82% of positive cases). Results: A total of 198 rearrangements was identified in 154 cases. CNVs were classified in three groups: i- CNVs previously known to be associated with ASD or ID (28/198, 14%), including 16p11.2, 15q13.3, 17p12 and 17q12; ii- CNVs including genes known to be associated with either ASD or ID (9/198, 4.5%); iii- CNVs of unknown significance (161/198, 81.3%). Conclusions: Our study confirmed that array-CGH analysis is able to detect the underlying genetic cause in about 18% of ASD or ID patients, highlighting it as an essential diagnostic tool for patients assessment. Overall, a prevalence of duplications with respect to deletions was observed (62% and 38% respectively) but among the deleted cases an enrichment of microdeletions in ASD cases (p=0.03) is present. Furthermore, we shown a prevalence of multiple CNVs in ASD cases compared to ID (p=0.05), pointing out the complex nature of ASD.