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Abstract：
The study was conducted between 2018 and 2020. From a cohort of 113 hearing impaired (HI), five non-DFNB12 probands identified with heterozygous CDH23 variants were subjected to exome analysis. This resolved the etiology of hearing loss (HL) in four South Indian assortative mating families. Six variants, including three novel ones, were identified in four genes: PNPT1 p.(Ala46Gly) and p.(Asn540Ser), MYO15A p.(Leu1485Pro) and p.(Tyr1891Ter), PTPRQ p.(Gln1336Ter), and SLC12A2 p.(Pro988Ser). Compound heterozygous PNPT1 variants were associated with DFNB70 causing prelingual profound sensorineural hearing loss (SNHL), vestibular dysfunction, and unilateral progressive vision loss in one family. In the second family, MYO15A variants in the myosin motor domain, including a novel variant, causing DFNB3, were found to be associated with prelingual profound SNHL. A novel PTPRQ variant was associated with postlingual progressive sensorineural/mixed HL and vestibular dysfunction in the third family with DFNB84A. In the fourth family, the SLC12A2 novel variant was found to segregate with severe-to-profound HL causing DFNA78, across three generations. Our results suggest a high level of allelic, genotypic, and phenotypic heterogeneity of HL in these families. This study is the first to report the association of PNPT1, PTPRQ, and SLC12A2 variants with HL in the Indian population.
摘要：
这项研究是在2018年至2020年之间进行的。从113名听力受损（HI）的队列中，用杂合CDH23变体鉴定的五个非DFNB12先证物进行外显子组分析。这解决了南印度四个交配家庭的听力损失（HL）的病因。六种变体,包括三部小说，在四个基因中鉴定：PNPT1p。（Ala46Gly）和p。（Asn540Ser），MYO15Ap.(Leu1485Pro)和p.(Tyr1891Ter)，PTPRQp.(Gln1336Ter),和SLC12A2p.（Pro988Ser）。复合杂合子PNPT1变异体与DFNB70相关，导致舌前深度感觉神经性听力损失（SNHL），前庭功能障碍,一个家庭的单侧进行性视力丧失。在第二个家庭，肌球蛋白运动域中的MYO15A变体，包括一个新颖的变体，导致DFNB3，被发现与语前深度SNHL有关。在DFNB84A的第三家族中，一种新的PTPRQ变体与舌后进行性感觉神经性/混合性HL和前庭功能障碍有关。在第四个家庭中，发现SLC12A2新变体与严重至严重的HL分离，导致DFNA78，在三代中。我们的结果表明高水平的等位基因，基因型，和这些家庭中HL的表型异质性。本研究首次报道了PNPT1、PTPRQ、和SLC12A2变异与HL在印度人口。
