Chromosomal microarray analyses from 5,778 patients with neurodevelopmental disorders and congenital anomalies in Brazil

ABSTRACT Chromosomal microarray analysis (CMA) has been recommended and practiced routinely since 2010 in USA and Europe as the first-tier cytogenetic test for patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies. However, in Brazil, the use of CMA is still limited, due to its high cost and complexity of the combination of private and public health systems. Although the country has one of the world largest single payer public healthcare system, nearly all patients referred for CMA come from the private sector. This reflects on the small number of CMA studies in Brazilian cohorts. This study is by far the largest Brazilian cohort (n=5,788) studied by CMA and results from a joint collaboration formed by the University of Sao Paulo and three private genetic diagnostic centers to investigate the genetic bases of neurodevelopmental disorders and congenital abnormalities. It is common practice to investigate the inheritance of VUS; however, our results indicate an extremely low cost-benefit of this approach, and strongly suggest that in cases of limited budget, investigation of the parents of VUS carriers using CMA should not be prioritized. Another aspect discussed is the classification of variants of low penetrance, once CNV classification is mostly designed to Mendelian or highly-penetrant variants.