Copy number variations in a Brazilian cohort with autism spectrum disorders highlight the contribution of cell adhesion genes

Author(s):Show less -

Samogy Costa, Claudia Ismania ^[1] ; da Silva Montenegro, Eduarda Morgana ^[1] ; Zarrei, Mehdi ^[2] ; Moreira, Eloisa de Sa ^[1] ; Wahys Silva, Isabela Maya ^[1] ; Scliar, Marilia de Oliveira ^[1] ; Wang, Jaqueline Yu Ting ^[1] ; Zachi, Elaine Cristina ^[1] ; Branco, Elisa Varella ^[1] ; da Costa, Silvia Souza ^[1] ; Vilaca Lourenco, Naila Cristina ^[1] ; Vianna-Morgante, Angela Maria ^[1] ; Rosenberg, Carla ^[1] ; Victorino Krepischi, Ana Cristina ^[1] ; Scherer, Stephen W. ^{[3, 2, 4]} ; Passos-Bueno, Maria Rita ^[1]

Affiliation

^[1] Univ Sao Paulo, Ctr Estudos Genoma Humano & Celulas Tronco, Inst Biociencias, Dept Genet & Biol Evolut, Sao Paulo, SP - Brazil

^[2] Hosp Sick Children, Ctr Appl Genom Genet & Genome Biol, Toronto, ON - Canada

^[3] Univ Toronto, Dept Mol Genet, Toronto, ON - Canada

^[4] Univ Toronto, McLaughlin Ctr, Toronto, ON - Canada

• Document type: Journal article
• Source: Clinical Genetics; v. 101, n. 1 NOV 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/19521-7 - Characterization of the genetic architecture of neurodevelopmental disorders using Duchenne Muscular Dystrophy as a model
• Grantee: Claudia Ismania Samogy Costa
• Support Opportunities: Scholarships in Brazil - Doctorate