Medical Genetics Center, Southwest Hospital, Army Medical University, Chongqing, China.
Department of Otorhinolaryngology Head and Neck Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Mol Genet Genomic Med. 2019 Jun;7(6):e685. doi: 10.1002/mgg3.685. Epub 2019 Apr 23.
Genetic variants in TMPRSS3 have been causally linked to autosomal recessive nonsyndromic hearing loss (HL) at the DFNB8 and DFNB10 loci. These variants include both single nucleotide and copy number variations (CNVs). In this study, we aim to identify the genetic cause in three Chinese subjects with prelingual profound sensorineural HL.
We applied targeted genomic enrichment and massively parallel sequencing to screen 110 genes associated with nonsyndromic HL in the three affected subjects. CNVplex analysis and polymerase chain reaction (PCR) were performed for CNV detection.
We identified biallelic variations in TMPRSS3 including a novel complex genomic rearrangement and a novel missense mutation, c.551T>C. We have mapped the breakpoints of the genomic rearrangement and showed that it consisted of two deletions and an inversion encompassing exon 3 to exon 9 of TMPRSS3.
Our study expanded the mutational spectrum of TMPRSS3 to include complex genomic rearrangements. It showcased the importance of an integrative approach to investigate CNVs and their contribution to HL.
TMPRSS3 中的遗传变异与常染色体隐性非综合征性听力损失（HL）的 DFNB8 和 DFNB10 位点有关。这些变体包括单核苷酸和拷贝数变异（CNVs）。在这项研究中，我们旨在确定 3 名患有语前深度感觉神经性 HL 的中国受试者的遗传原因。
我们应用靶向基因组富集和大规模平行测序技术筛选了 3 名受影响受试者中与非综合征性 HL 相关的 110 个基因。进行了 CNVplex 分析和聚合酶链反应（PCR）以检测 CNV。
我们在 TMPRSS3 中发现了双等位基因变异，包括一个新的复杂基因组重排和一个新的错义突变 c.551T>C。我们已经定位了基因组重排的断点，并表明它由两个缺失和一个包含 TMPRSS3 外显子 3 到外显子 9 的倒位组成。
我们的研究扩展了 TMPRSS3 的突变谱，包括复杂的基因组重排。它展示了综合方法研究 CNV 及其对 HL 贡献的重要性。
