Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha, China.
Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha, China.
Clin Chim Acta. 2022 Jul 1;532:53-60. doi: 10.1016/j.cca.2022.05.020. Epub 2022 May 28.
Hearing loss is a group of diseases with high genetic heterogeneity. About 160 genes have been reported to be associated with hereditary hearing loss.
113 families with hearing loss were collected, and WES was used to detect SNV, InDel, CNV and mitochondrial gene variants. For some probands with negative WES test results, the copy number of STRC and OTOA were determined by using real-time fluorescence quantitative PCR.
Pathogenic or likely pathogenic variants were found in 54 probands, of which 98% (53/54) were SNVs or InDels and 2% (1/54) were CNVs, a positive rate of 48%. 16 families (14%) were detected with candidate variants of uncertain significance. 19 novel pathogenic or likely pathogenic variants and 22 candidate variants of uncertain significance were identified in this study. The most common hearing loss gene in the families was GJB2, accounting for 28% (15/53), followed by SLC26A4 and MYO15A, accounting for 21% (11/53) and 11% (6/53), respectively. Heterozygous gene deletion was detected in 3 probands, including 2 with STRC and 1 with OTOA in 43 families with WES negative test.
Genetic etiology was clarified in 54 families. All of these findings broadened the mutation spectrum of hearing loss genes, thus providing new variant information for the future diagnosis of patients with hearing loss.
听力损失是一组具有高度遗传异质性的疾病。据报道，约有 160 个基因与遗传性听力损失有关。
收集了 113 个听力损失家系，采用 WES 检测 SNV、InDel、CNV 和线粒体基因变异。对于 WES 检测结果阴性的部分先证者，采用实时荧光定量 PCR 检测 STRC 和 OTOA 的拷贝数。
在 54 个先证者中发现了致病性或可能致病性变异，其中 98%（53/54）为 SNV 或 InDel，2%（1/54）为 CNV，阳性率为 48%。检测到 16 个家系（14%）存在意义未明的候选变异。本研究共发现 19 个新的致病性或可能致病性变异和 22 个意义未明的候选变异。家系中最常见的听力损失基因是 GJB2，占 28%（15/53），其次是 SLC26A4 和 MYO15A，分别占 21%（11/53）和 11%（6/53）。在 3 个先证者中检测到杂合性基因缺失，包括 2 个 STRC 和 1 个 OTOA，在 43 个 WES 检测结果阴性的家系中。
在 54 个家系中明确了遗传病因。所有这些发现拓宽了听力损失基因的突变谱，为未来听力损失患者的诊断提供了新的变异信息。
