Matos Tiago D, Simões-Teixeira Helena, Caria Helena, Rosa Helena, O'Neill Assunção, Fialho Graça
Faculty of Science, Centre for Biodiversity, Functional, and Integrative Genomics (BioFIG), University of Lisbon, Lisbon, Portugal.
Genet Test Mol Biomarkers. 2010 Feb;14(1):141-4. doi: 10.1089/gtmb.2009.0103.
Mutations in the GJB2 gene account for up to 50% of hereditary nonsyndromic hearing loss in several populations. Over 200 mutations are already described in this gene, and three of them, c.35delG, c.167delT, and c.235delC, are the most frequent in Caucasians, Ashkenazi Jews, and Asians, respectively. Most of GJB2 hearing loss-related mutations are recessive, but a few dominant alleles have also been described. Apart from the clearly pathogenic mutations, there are some other variants whose pathogenicity is still controversial, such as p.Met34Thr, p.Val37Ile, p.Arg127His, and p.Val153Ile. The p.Arg127His allele has been found in some mono- and biallelic hearing-impaired patients from several countries. In this article we report on some Portuguese patients harboring this mutation. Taking into consideration the analysis of these Portuguese cases as well as the genetic and functional data regarding p.Arg127His available in the literature, we conclude that this variant may be a cause of hearing loss depending on environmental factors and/or genetic background.
GJB2基因的突变在一些人群中导致了高达50%的遗传性非综合征性听力损失。该基因已发现200多种突变，其中三种，即c.35delG、c.167delT和c.235delC，分别在高加索人、德系犹太人及亚洲人中最为常见。大多数与GJB2听力损失相关的突变是隐性的，但也有一些显性等位基因被描述过。除了明确的致病性突变外，还有一些其他变异，其致病性仍存在争议，如p.Met34Thr、p.Val37Ile、p.Arg127His和p.Val153Ile。在来自几个国家的一些单等位基因和双等位基因听力受损患者中发现了p.Arg127His等位基因。在本文中，我们报告了一些携带此突变的葡萄牙患者。考虑到对这些葡萄牙病例的分析以及文献中有关p.Arg127His的遗传和功能数据，我们得出结论，根据环境因素和/或遗传背景，这种变异可能是听力损失的一个原因。
