Chromosomal microarray analyses from 5778 patients with neurodevelopmental disorders and congenital anomalies in Brazil.

Autor: Krepischi ACV; The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, São Paulo, ZIP Code 05508-090, Brazil.; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Villela D; Diagnósticos da América S.A., DASA, São Paulo, Brazil., da Costa SS; The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, São Paulo, ZIP Code 05508-090, Brazil., Mazzonetto PC; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Schauren J; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Migliavacca MP; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Milanezi F; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Santos JG; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Guida G; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Guarischi-Sousa R; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Campana G; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Kok F; Mendelics, São Paulo, SP, Brazil., Schlesinger D; Mendelics, São Paulo, SP, Brazil., Kitajima JP; Mendelics, São Paulo, SP, Brazil., Campagnari F; Mendelics, São Paulo, SP, Brazil., Bertola DR; The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, São Paulo, ZIP Code 05508-090, Brazil.; Instituto da Criança Do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., Vianna-Morgante AM; The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, São Paulo, ZIP Code 05508-090, Brazil., Pearson PL; The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, São Paulo, ZIP Code 05508-090, Brazil., Rosenberg C; The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, São Paulo, ZIP Code 05508-090, Brazil. carlarosenberg@ib.usp.br.; Diagnósticos da América S.A., DASA, São Paulo, Brazil. carlarosenberg@ib.usp.br.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Sep 07; Vol. 12 (1), pp. 15184. Date of Electronic Publication: 2022 Sep 07.
DOI: 10.1038/s41598-022-19274-6
Abstrakt: Chromosomal microarray analysis (CMA) has been recommended and practiced routinely since 2010 both in the 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 in integrating the results from both the private and public health systems. Although Brazil has one of the world's largest single-payer public healthcare systems, nearly all patients referred for CMA come from the private sector, resulting in only a small number of CMA studies in Brazilian cohorts. To date, this study is by far the largest Brazilian cohort (n = 5788) studied by CMA and is derived from a joint collaboration formed by the University of São Paulo and three private genetic diagnostic centers to investigate the genetic bases of neurodevelopmental disorders and congenital abnormalities. We identified 2,279 clinically relevant CNVs in 1886 patients, not including the 26 cases of UPD found. Among detected CNVs, the corresponding frequency of each category was 55.6% Pathogenic, 4.4% Likely Pathogenic and 40% VUS. The diagnostic yield, by taking into account Pathogenic, Likely Pathogenic and UPDs, was 19.7%. Since the rational for the classification is mostly based on Mendelian or highly penetrant variants, it was not surprising that a second event was detected in 26% of those cases of predisposition syndromes. Although it is common practice to investigate the inheritance of VUS in most laboratories around the world to determine the inheritance of the variant, our results indicate an extremely low cost-benefit of this approach, and strongly suggest that in cases of a limited budget, investigation of the parents of VUS carriers using CMA should not be prioritized.
(© 2022. The Author(s).)
Databáze: MEDLINE
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