Chromosomal Microarray Diagnostic Yield and Copy Number Variants in a Clinically Well-Characterized Cohort with...

Background/Objectives: Chromosomal microarray analysis (CMA) is widely used in the genetic evaluation of autism spectrum disorder (ASD), yet its diagnostic contribution in clinically nonsyndromic ASD, particularly in Brazilian populations, remains insufficiently characterized. This study aimed to determine the diagnostic yield of CMA and characterize clinically relevant copy number variants (CNVs) in a cohort of individuals with clinically nonsyndromic ASD from southern Brazil. Methods: In this observational cohort study, 215 individuals with clinically diagnosed ASD underwent high-resolution CMA using the Agilent CGH + SNP Array 180K platform. Individuals with dysmorphic features, known or suspected genetic syndromes, major congenital malformations, epilepsy, or macrocephaly/microcephaly were excluded. CNVs were classified according to American College of Medical Genetics and Genomics guidelines, and the diagnostic yield was compared with that of national and international reference cohorts using Fisher's exact test. Results: Pathogenic or likely pathogenic CNVs were identified in six individuals, corresponding to a diagnostic yield of 2.8% (95% CI, 1.3-6.1%). These included deletions at 2q11.1-q11.2, 2p16.3 (NRXN1), 15q11.2 (BP1-BP2), and 3q29, and duplications at 16p11.2 and 6p22.3-p22.2. Although the diagnostic yield was lower than that reported in phenotypically heterogeneous ASD cohorts, it did not differ significantly from yields observed in comparably selected nonsyndromic subgroups. Conclusions: CMA identified clinically relevant recurrent CNVs at neurodevelopmental loci even in a clinically nonsyndromic ASD cohort. The comparatively low diagnostic yield highlights the substantial influence of clinical and phenotypic selection on the diagnostic contribution of CMA.