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Genomic study of nonsyndromic hearing loss in unaffected individuals: Frequency of pathogenic and likely pathogenic variants in a Brazilian cohort of 2,097 genomes

Authors :
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)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

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.

Details

Language :
English
ISSN :
16648021
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Genetics
Publication Type :
Academic Journal
Accession number :
edsdoj.725ec5d20214dbdb3f344e4e8fcf56f
Document Type :
article
Full Text :
https://doi.org/10.3389/fgene.2022.921324