Universidade Federal do Rio de Janeiro (UFRJ), Hospital Universitário Clementino Fraga Filho (HUCFF), Rio de Janeiro, RJ, Brazil.
Universidade Federal do Rio de Janeiro (UFRJ), Hospital Universitário Clementino Fraga Filho (HUCFF), Rio de Janeiro, RJ, Brazil.
Braz J Otorhinolaryngol. 2019 Jan-Feb;85(1):92-98. doi: 10.1016/j.bjorl.2017.10.013. Epub 2017 Nov 21.
In different parts of the world, mutations in the GJB2 gene are associated with nonsyndromic hearing loss, and the homozygous 35delG mutation (p.Gly12Valfs*2) is a major cause of hereditary hearing loss. However, the 35delG mutation is not equally prevalent across ethnicities, making it important to study other mutations, especially in multiethnic countries such as Brazil.
This study aimed to identify different mutations in the GJB2 gene in patients with severe to profound nonsyndromic sensorineural hearing loss of putative genetic origin, and who were negative or heterozygote for the 35delG mutation.
Observational study that analyzed 100 ethnically characterized Brazilian patients with nonsyndromic severe to profound sensorineural hearing loss, who were negative or heterozygote for the 35delG mutation. GJB2 mutations were detected by DNA-based sequencing in this population. Participants' ethnicities were identified as Latin European, Non-Latin European, Jewish, Native, Turkish, Afro-American, Asian and Others.
Sixteen participants were heterozygote for the 35delG mutation; 14 participants, including three 35delG heterozygote's, had nine different alterations in the GJB2 gene. One variant, p.Ser199Glnfs9, detected in two participants, was previously unreported. Three variants were pathogenic (p.Trp172, p.Val167Met, and p.Arg75Trp), two were non-pathogenic (p.Val27Ile and p.Ile196Thr), and three variants were indeterminate (p.Met34Thr, p.Arg127Leu, and p.Lys168Arg). Three cases of compound heterozygosity were detected: p.[(Gly12Valfs2)];[(Trp172)], p.(Gly12Valfs*2)[(Met34Thr)], and p.[(Gly12Valfs2)(;)[(Ser199Glnfs9)]).
This study detected previously unclassified variants and one case of previously unreported compound heterozygosity.
在世界不同地区，GJB2 基因突变与非综合征型听力损失有关，纯合 35delG 突变（p.Gly12Valfs*2）是遗传性听力损失的主要原因。然而，35delG 突变在不同种族中的流行程度并不相同，因此研究其他突变，尤其是在像巴西这样的多民族国家，非常重要。
本研究旨在鉴定具有遗传起源的重度至极重度非综合征型感音神经性听力损失且 35delG 突变阴性或杂合子的患者的 GJB2 基因中的不同突变。
对 100 名具有非综合征型重度至极重度感音神经性听力损失且 35delG 突变阴性或杂合子的巴西患者进行了观察性研究。在该人群中通过基于 DNA 的测序检测 GJB2 突变。参与者的种族特征为拉丁欧洲人、非拉丁欧洲人、犹太人、本地人、土耳其人、非裔美国人、亚洲人和其他人。
16 名参与者为 35delG 突变杂合子；14 名参与者，包括 3 名 35delG 杂合子，在 GJB2 基因中有 9 种不同的改变。两个参与者中检测到的一个变体 p.Ser199Glnfs9 之前未报道过。三个变体是致病性的（p.Trp172、p.Val167Met 和 p.Arg75Trp），两个是非致病性的（p.Val27Ile 和 p.Ile196Thr），三个是不确定的（p.Met34Thr、p.Arg127Leu 和 p.Lys168Arg）。检测到三种复合杂合性：p.[(Gly12Valfs2)];[(Trp172)]、p.[(Gly12Valfs2)(;)[(Met34Thr)]] 和 p.[(Gly12Valfs2)(;)[(Ser199Glnfs*9)]]。
本研究检测到以前未分类的变体和一种以前未报道的复合杂合性。
