학술논문
Genomic study of nonsyndromic hearing loss in unaffected individuals: Frequency of pathogenic and likely pathogenic variants in a Brazilian cohort of 2,097 genomes
Document Type
article
Author
Caio Robledo D’ Angioli Costa Quaio; Antonio Victor Campos Coelho; Livia Maria Silva Moura; Rafael Lucas Muniz Guedes; Kelin Chen; Jose Ricardo Magliocco Ceroni; Renata Moldenhauer Minillo; Marcel Pinheiro Caraciolo; Rodrigo de Souza Reis; Bruna Mascaro Cordeiro de Azevedo; Maria Soares Nobrega; Anne Caroline Barbosa Teixeira; Matheus Martinelli Lima; Thamara Rayssa da Mota; Marina Cadena da Matta; Gabriela Borges Cherulli Colichio; Aline Lulho Roncalho; Ana Flavia Martinho Ferreira; Gabriela Pereira Campilongo; Eduardo Perrone; Luiza do Amaral Virmond; Carolina Araujo Moreno; Joana Rosa Marques Prota; Marina de França; Murilo Castro Cervato; Tatiana Ferreira de Almeida; Joao Bosco de Oliveira Filho
Source
Frontiers in Genetics, Vol 13 (2022)
Subject
Language
English
ISSN
1664-8021
Abstract
Hearing loss (HL) is a common sensory deficit in humans and represents an important clinical and social burden. We studied whole-genome sequencing data of a cohort of 2,097 individuals from the Brazilian Rare Genomes Project who were unaffected by hearing loss to investigate pathogenic and likely pathogenic variants associated with nonsyndromic hearing loss (NSHL). We found relevant frequencies of individuals harboring these alterations: 222 heterozygotes (10.59%) for sequence variants, 54 heterozygotes (2.58%) for copy-number variants (CNV), and four homozygotes (0.19%) for sequence variants. The top five most frequent genes and their corresponding combined allelic frequencies (AF) were GJB2 (AF = 1.57%), STRC (AF = 1%), OTOA (AF = 0.69%), TMPRSS3 (AF = 0.41%), and OTOF (AF = 0.29%). The most frequent sequence variant was GJB2:c.35del (AF = 0.72%), followed by OTOA:p. (Glu787Ter) (AF = 0.61%), while the most recurrent CNV was a microdeletion of 57.9 kb involving the STRC gene (AF = 0.91%). An important fraction of these individuals (n = 104; 4.96%) presented variants associated with autosomal dominant forms of NSHL, which may imply the development of some hearing impairment in the future. Using data from the heterozygous individuals for recessive forms and the Hardy–Weinberg equation, we estimated the population frequency of affected individuals with autosomal recessive NSHL to be 1:2,222. Considering that the overall prevalence of HL in adults ranges from 4–15% worldwide, our data indicate that an important fraction of this condition may be associated with a monogenic origin and dominant inheritance.