Targeted Resequencing of Deafness Genes Reveals a FounderMYO15AVariant in Northeastern Brazil

Abstract

Identifying the genetic etiology in a person with hearing loss (HL) is challenging due to the extreme genetic heterogeneity in HL and the population specific variability. In this study, after excluding GJB2 variants, targeted resequencing of 180 deafness-related genes revealed the causative variants in 11 of 19 (58%) Brazilian probands with autosomal recessive HL. Identified pathogenic variants were in MYO15A (10 families) and CLDN14 (1 family). Remarkably, the MYO15A p.(Val1400Met) variant was identified in 8 families from the city of Monte Santo in the Northeast region of Brazil. Haplotype analysis of this variant was consistent with a single founder. No other cases with this variant were detected among 105 simplex cases from other cities of Northeastern Brazil, suggesting that this variant is confined to a geographical region. This study suggests that it is feasible to develop population-specific screening for deafness variants once causative variants are identified in different geographical groups.

Targeted next‐generation sequencing of deaf patients from Southwestern China

“…This might be an explanation for the identification of several “VUS” variants in our cohorts of deaf patients. Several studies have shown that people in different regions have different genetic backgrounds, especially for ethnicities (Liu et al, 2002; Manzoli et al, 2016; Miyagawa et al, 2013; Yan et al, 2016). This suggested that allele frequency database of deafness genes in local people should be established.…”

The Segregation of p.Arg68Ter-CLDN14 Mutation in a Syrian Deaf Family, Phenotypic Variations, and Comparative Analysis with the GJB2 Gene

“…So far, fourteen mutations in the CLDN14 gene have been associated with ARSNHL [3,[7][8][9][10][11][12][13][14][15][16][17]. The highest contribution and number of mutations have been reported in the Pakistani population, where the prevalence of CLDN14 pathogenic variants was estimated to be 2.25% of deaf individuals [7].…”

“…The highest contribution and number of mutations have been reported in the Pakistani population, where the prevalence of CLDN14 pathogenic variants was estimated to be 2.25% of deaf individuals [7]. It is worth noting that even though there is phenotypic variability associated with certain mutations, the impact of CLDN14 mutations tends to be more severe at higher frequencies, with moderate to severe phenotypes reported at low frequencies, while severe to profound phenotypes often exhibited at higher frequencies [3,7,8,[10][11][12][13][14].…”

Molecular study of hearing loss in Minas Gerais, Brazil

“… 9 Besides, molecular diagnosis is more restricted in cientific researches, and the high genetic heterogeneity of non-syndromic hearing loss is a complicating factor. 10 …”