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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. [ABSTRACT FROM AUTHOR]

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.

Hearing loss caused by environmental or genetic factors concerns more than 10% of the world's population, leading to disability and considerable deterioration of the quality of life for deaf people. On the average, one in 1000 children is born deaf with 50-60% of the cases having a genetic cause. Nonsyndromic hereditary deafness is a monogenic disease with uniquely high genetic heterogeneity. The prevalence of some forms of genetic deafness varies in different regions of the world and is determined, as for many other monogenic diseases, by the ethnic composition, isolation, founder and bottleneck effects, rate of consanguineous marriages, and potential heterozygote selective advantage. It is assumed that some social factors (a longstanding tradition of assortative marriages between deaf people combined with an increase in their social adaptation and genetic fitness) have contributed to a high prevalence of hearing loss caused by mutations in the GJB2 (C×26) gene. The breach of deep social isolation of the deaf some 300 years ago in Europe (and later in the United States) with the establishment of schools for the deaf teaching sign language as a common communication tool (linguistic homogamy) triggered these events. Computer simulation and comparative retrospective studies have shown that these social processes could have doubled the rate of GJB2 deafness in the United States over two centuries. The information about the sociodemographic structure of deaf communities in the past is extremely limited by the almost complete lack of the relevant archival data. Nevertheless, studies of the sociodemographic and medical genetic characteristics of deaf communities are now important for both predicting the prevalence of various hereditary deafness forms and understanding the impact of social factors on evolutionary processes in human populations. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The following authors are employees (received salary and other bonuses) of Hospital Israelita Albert Einstein: CQ; AC; LM; RG; KC; JC; RM; MC; RD; BA; MN; AT; ML; TM; MM; GC; AR; AF; GC; EP; LV; CM; JP; MD; MC; TA; and JO., (Copyright © 2022 Quaio, Coelho, Moura, Guedes, Chen, Ceroni, Minillo, Caraciolo, Reis, Mascaro, Nobrega, Teixeira, Martinelli, Mota, Matta, Colichio, Roncalho, Ferreira, Campilongo, Perrone, Virmond, Moreno, Prota, França, Cervato, Almeida and Oliveira.)