Copy number variations in a Brazilian cohort with autism spectrum disorders highlight the contribution of cell adhesion genes
Claudia Ismania Samogy Costa, Eduarda Morgana da Silva Montenegro, Mehdi Zarrei, Eloisa De Sá Moreira, Isabela Mayá Wayhs Silva, Marília O. Scliar, Jaqueline Yu Ting Wang, Elaine Cristina Zachi, Elisa Varella Branco, Silvia Souza da Costa, Naila Cristina Vilaça Lourenço, Angela Maria Vianna‐Morgante, Carla Rosenberg, Ana Cristina Victorino Krepischi, Stephen W. Scherer, Maria Rita Passos‐Bueno
Abstract
Prediction of pathogenicity of rare copy number variations (CNVs), a genomic alteration known to contribute to the etiology of autism spectrum disorder (ASD), represents a serious limitation to interpreting genetic tests, particularly for genetic counseling purposes. Chromosomal microarray analysis (CMA) was conducted in a unique collection of 144 Brazilian individuals with ASD of strong European and African ancestries. Rare CNVs were detected in 39 patients: 41 of unknown significance (VUS), four pathogenic and one likely pathogenic CNVs (clinical yield of 4.1%; 5/122). Based on gene content and recurrence in three large cohorts [a Brazilian neurodevelopmental disorder cohort, the autism MSSNG cohort, and the Canadian-based Centre for Applied Genomics microarray database], this work strengthened the pathogenicity of 14 genes (FAT1, CAMK4, BIRC6, DPP6, CSMD1, CTNNA3, CDH8/CDH11, CDH13, OR1C1, CNTN6, CNTNAP4, FGF2 and PTPRN2) within 14 CNVs. Notably, enrichment of cell adhesion proteins to ASD etiology was identified (p < 0.05), highlighting the importance of these gene families in the etiology of ASD.