Department of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.
Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, 410008, Hunan, China.
Eur Arch Otorhinolaryngol. 2020 Dec;277(12):3331-3339. doi: 10.1007/s00405-020-06050-3. Epub 2020 May 23.
The identification of gene mutations enables more appropriate genetic counseling and proper medical management for EVA patients. The purpose of this study was to validate the accuracy and sensitivity of our method for comprehensive mutation detection in EVA, and summarize these data to explore a more accurate and convenient genetic diagnosis method.
A multiplex PCR sequencing panel was designed to capture the exons of three known EVA-associated genes (SLC26A4, KCNJ10, and FOXI1), and NGS was conducted in 17 Chinese families with EVA.
A total of 16 SLC26A4 variants were found in 21 probands with bilateral EVA, including three novel variants (c.416G>A, c.823G>A and c.1027G>C), which were not reported in the dbSNP, gnomAD database, and ClinVar databases. One patient carried a FOXI1 variant (heterozygous, c.214C>A) and one patient carried a KCNJ10 variant (heterozygous, c.1054C>A), both of which were novel variants. Biallelic potential pathogenic variants were detected in 21/21patient samples, leading to a purported diagnostic rate of 100%. All results were verified by Sanger sequencing.
This result supplemented the mutation spectrum of EVA, and supports that combined multiple PCR-targeted enrichment, and NGS is a valuable molecular diagnostic tool for EVA, and is suitable for clinical application.
基因突变的鉴定能够为 EVA 患者提供更合适的遗传咨询和适当的医疗管理。本研究旨在验证我们用于 EVA 全面突变检测的方法的准确性和灵敏度，并总结这些数据，以探索更准确、更方便的遗传诊断方法。
设计了一个多重 PCR 测序panel，以捕获三个已知与 EVA 相关的基因（SLC26A4、KCNJ10 和 FOXI1）的外显子，对 17 个有 EVA 家系的患者进行了 NGS 检测。
在 21 名双侧 EVA 的先证者中发现了 16 个 SLC26A4 变异，包括三个新的变异（c.416G>A、c.823G>A 和 c.1027G>C），这些变异未在 dbSNP、gnomAD 数据库和 ClinVar 数据库中报道。一名患者携带 FOXI1 变异（杂合子，c.214C>A），一名患者携带 KCNJ10 变异（杂合子，c.1054C>A），均为新的变异。在 21/21 名患者样本中检测到双等位基因潜在致病性变异，假定诊断率为 100%。所有结果均通过 Sanger 测序验证。
该结果补充了 EVA 的突变谱，支持联合多重 PCR 靶向富集和 NGS 是一种有价值的 EVA 分子诊断工具，适合临床应用。
