TECTA突变谱的更新：一项范围综述

文献信息

中文摘要

背景/目的： TECTA基因变异是导致累及中频范围的非综合征性先天性听力损失的最常见原因之一。TECTA基因位于染色体11q22-q24，编码α-盖膜蛋白（α-tectorin），即盖膜的一种非胶原性蛋白。TECTA的致病性变异相对罕见，且已报道众多变异，使清晰且可识别的临床表型的界定变得复杂。本范围综述旨在对已知的导致常染色体显性遗传性感音神经性听力损失（ADSNHL）的TECTA变异及其相关听力学表型提供最新概述。方法：按照“系统综述和荟萃分析优先报告条目（PRISMA）”的范围综述标准，使用PubMed、Scopus、Google Scholar和MEDLINE数据库对与TECTA变异相关听力损失的英文文献进行了综述。结果：共有18项研究符合全部纳入标准。在合并同一cDNA水平变异的重复报告后，共识别出44个独特的TECTA变异。其中，14个被分类为致病性或可能致病性（P/LP），9个为意义不明确的变异（VUS），其余21个的分类为冲突、良性/可能良性或不可获得。基于结构域的分析显示变异显著集中于ZA结构域（21个变异，47.73%），其次为ZP结构域（14个变异，31.82%）和ENT结构域（5个变异，11.36%）。有32次变异出现被报道与中频听力损失相关，12次与高频听力损失相关。15次变异出现被报道为稳定性听力损失，而13次被报道为进展性听力损失。结论：识别和表征与听力损失相关的新遗传变异对于改善表型-基因型相关性至关重要。听力损失遗传病因的早期识别正变得越来越重要，尤其是考虑到近期儿童听力损失基因治疗的进展。

英文摘要

Background/Objectives: The TECTA gene variant is one of the most common causes of nonsyndromic congenital hearing loss affecting the mid-frequency range. Situated on chromosome 11q22-q24, the TECTA gene encodes α-tectorin, a non-collagenous protein of the tectorial membrane. Pathogenetic variants of TECTA are relatively rare, and numerous variants have been described, complicating the delineation of a clear and recognizable clinical phenotype. This scoping review aims to provide an up-to-date overview of the known TECTA variants causing autosomal dominant sensorineural hearing loss (ADSNHL) and their associated audiological phenotypes. Methods: A review of the English-language literature on hearing loss associated with TECTA variants was conducted using PubMed, Scopus, Google Scholar, and MEDLINE databases, in accordance with the "Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)" criteria for scoping review. Results: Eighteen studies met all inclusion criteria. Overall, 44 unique TECTA variants were identified after recurrent reports of the same cDNA-level variant were consolidated. Of these, 14 were classified as pathogenic or likely pathogenic (P/LP), 9 as variants of uncertain significance (VUS), while the remaining 21 had conflicting, benign/likely benign, or unavailable classification. Domain-based analysis showed a marked prevalence of variants in the ZA domain (21 variants, 47.73%), followed by the ZP domain (14 variants, 31.82%) and the ENT domain (5 variants, 11.36%). Thirty-two variant occurrences were reported in association with hearing loss in the mid frequencies and 12 in the high frequencies. Stable hearing loss was reported for 15 variant occurrences, whereas progressive hearing loss was reported for 13. Conclusions: The identification and characterization of novel genetic variants associated with hearing loss are essential for improving phenotype-genotype correlations. Early identification of the genetic etiology of hearing loss is becoming increasingly important, particularly in light of recent advances in gene therapy for pediatric hearing loss.