Genetic heterogeneity in autosomal recessive hearing loss: a survey of Brazilian families.

Autor:	Antunes LN; Centro de Pesquisas sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil., Dias AMM; Centro de Pesquisas sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil., Schiavo BC; Centro de Pesquisas sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil., Mendes BCA; Divisão de Educação e Reabilitação dos Distúrbios da Comunicação da Pontifícia Universidade Católica de São Paulo, São Paulo, Brazil., Bertola DR; Centro de Pesquisas sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.; Unidade de Genética do Instituto da Criança, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Lezirovitz K; Laboratório de Otorrinolaringologia/LIM32 - Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Mingroni-Netto RC; Centro de Pesquisas sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2024 Oct 21; Vol. 15, pp. 1409306. Date of Electronic Publication: 2024 Oct 21 (Print Publication: 2024).
DOI:	10.3389/fgene.2024.1409306
Abstrakt:	Introduction: Hearing loss is a frequent sensory impairment type in humans, with about 50% of prelingual cases being attributed to genetic factors. Autosomal recessive hearing loss (ARHL) exhibits great locus heterogeneity and is responsible for 70%-80% of hereditary nonsyndromic cases. Methods: A total of 90 unrelated Brazilian individuals were selected for having hearing loss of presumably autosomal recessive inheritance, either born from consanguineous marriages or belonging to families with two or more affected individuals in the sibship and most cases were of normal hearing parents. In all cases, common pathogenic variants in GJB2 (c.35delG), GJB6 [del(GJB6-D13S1830) and del(GJB6-D13S1854)] and MT-RNR1 (m.1555A>G) were discarded and most were previously assessed by complete Sanger sequencing of GJB2 . Their genetic material was analyzed through next-generation sequencing, targeting 99 hearing loss-related genes and/or whole exome sequencing. Results: In 32 of the 90 probands (36,7%) causative variants were identified, with autosomal recessive inheritance confirmed in all, except for two cases due to dominant variants ( SIX1 and P2RX2 ). Thirty-nine different causative variants were found in 24 different known hearing loss-associated genes, among which 10 variants are novel, indicating wide genetic heterogeneity in the sample, after exclusion of common pathogenic variants. Despite the genetic heterogeneity, some genes showed greater contribution: GJB2 , CDH23 , MYO15A , OTOF , and USH2A . Conclusion: The present results confirmed that next-generation sequencing is an effective tool for identifying causative variants in autosomal recessive hearing loss. To our knowledge, this is the first report of next-generation sequencing being applied to a large cohort of pedigrees with presumable autosomal recessive hearing loss in Brazil and South America. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Antunes, Dias, Schiavo, Mendes, Bertola, Lezirovitz and Mingroni-Netto.)
Databáze:	MEDLINE
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