PDF(Pubmed)
Abstract：
Hearing impairment, a rare inherited condition, is notably prevalent in populations with high rates of consanguinity. The most common form observed globally is autosomal recessive non-syndromic hearing loss. Despite its prevalence, this genetic disorder is characterized by a substantial genetic diversity, making diagnosis and screening challenging. The emergence of advanced next-generation sequencing (NGS) technologies has significantly advanced the discovery of genes and variants linked to various conditions, such as hearing loss. In this study, our objective was to identify the specific variant causing hearing loss in a family from Syria using clinical exome sequencing. The proband in the family exhibited profound deafness as shown by pure-tone audiometry results. The analysis of the different variants obtained by NGS revealed the presence of a nonsense mutation within the CLDN14 gene. Through Sanger sequencing, we verified that this variant segregates with the disease and was not present in the control population. Moreover, we conducted a comprehensive review of all reported deafness-related CLDN14 mutations and their associated phenotypes. Furthermore, we endeavored to carry out a comparative analysis between the CLDN14 and GJB2 genes, with the objective of identifying potential factors that could explain the notable discrepancy in mutation frequency between these two genes.
摘要：
听力障碍,一种罕见的遗传性疾病,在血缘关系率高的人群中尤为普遍。全球观察到的最常见形式是常染色体隐性非综合征性听力损失。尽管流行,这种遗传疾病的特征是大量的遗传多样性，诊断和筛查具有挑战性。先进的下一代测序（NGS）技术的出现大大推进了与各种条件相关的基因和变体的发现，比如听力损失。在这项研究中,我们的目的是通过临床外显子组测序,在一个来自叙利亚的家庭中鉴定导致听力损失的特定变异.纯音测听结果显示，家庭中的先证者表现出严重的耳聋。通过NGS获得的不同变体的分析揭示了CLDN14基因内无义突变的存在。通过Sanger测序,我们证实这种变异与疾病分离,在对照人群中不存在.此外，我们对所有报道的耳聋相关CLDN14突变及其相关表型进行了全面回顾.此外，我们努力在CLDN14和GJB2基因之间进行比较分析，目的是确定可以解释这两个基因之间突变频率显着差异的潜在因素。
