儿童听力损失相关基因变异：大型加拿大队列中的患病率。

Variants in Genes Associated with Hearing Loss in Children: Prevalence in a Large Canadian Cohort.

机构信息

Archie's Cochlear Implant Laboratory, Neuroscience & Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.

Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada.

出版信息

Laryngoscope. 2024 Aug;134(8):3832-3838. doi: 10.1002/lary.31373. Epub 2024 Mar 1.

DOI:10.1002/lary.31373

PMID:38426810

Abstract

OBJECTIVE

The objective of this study was to assess the prevalence of genetic variants associated with hearing loss in a large cohort of children in Canada using high throughput next generation sequencing (NGS).

METHODS

A total of 485 children with hearing loss underwent NGS testing with an 80 gene panel of syndromic and non-syndromic variants known to be associated with hearing loss. Genetic variants were classified as pathogenic, likely pathogenic, likely benign, benign, or variants of uncertain significance (VUS), according to the American College of Medical Genetics and Genomics guidelines.

RESULTS

Across the 80 genes tested, 923 variants, predominantly in 28 genes, were identified in 324 children. Pathogenic variants occurred in 19/80 (23.8%) of the hearing loss related genes tested and confirmed the etiology of hearing loss in 73/485 (15.1%) of children. GJB2 was the most prevalent gene, affecting 28/73 (38.4%) children with confirmed genetic hearing loss in our cohort. Most identified variants (748/923, 81.0%, in 76/80 genes) were of uncertain significance.

CONCLUSION

Genetic testing using NGS identified the etiology in approximately 15% of childhood hearing loss in a Canadian cohort which is lower than what is typically reported. GJB2 was the most common genetic cause of hearing loss. VUS are commonly identified, presenting clinical challenges for counseling.

LEVEL OF EVIDENCE

4 Laryngoscope, 134:3832-3838, 2024.

摘要

目的

本研究旨在通过高通量下一代测序（NGS）评估加拿大一大群儿童中与听力损失相关的遗传变异的流行率。

方法

共有 485 名听力损失儿童接受了 NGS 测试，该测试使用了 80 个基因的综合测试，其中包括与听力损失相关的综合征和非综合征变异。根据美国医学遗传学与基因组学学院的指南，遗传变异被分为致病性、可能致病性、可能良性、良性或意义不明的变异（VUS）。

结果

在测试的 80 个基因中，在 324 名儿童中发现了 923 个变体，主要集中在 28 个基因中。致病性变体出现在 80 个听力损失相关基因中的 19 个（23.8%），并在 485 名儿童中的 73 名（15.1%）中证实了听力损失的病因。GJB2 是最常见的基因，影响了我们队列中 73 名（38.4%）有明确遗传听力损失的儿童。大多数确定的变体（748/923，81.0%，在 76/80 个基因中）意义不明。