PDF(Pubmed)
Abstract：
Background: Mutations in the MYO6 gene have been associated with both autosomal dominant non-syndromic hearing loss (ADNSHL) and autosomal recessive non-syndromic hearing loss (ARNSHL), with a cumulative identification of 125 pathogenic variants. To investigate the underlying genetic factor within a Chinese family affected with heriditary hearing loss, prompted the utilization of high-throughput sequencing. Method: A detailed clinical investigation was performed. Genetic testing was performed by using target panel sequencing, and Sanger sequencing. Targeted sequencing identified the variants and Sanger sequencing was employed to validate segregation of the identified variants within family. Additionally, bioinformatics analysis was performed to strengthen our findings. Results: Clinical investigation revealed the family members were affected by progressive and sensorineural hearing loss with an onset around 8-10 years old. Furthermore, genetic testing identified novel MYO6 variants, c.[2377T>G; 2382G>T] p.[Trp793Gly; Lys794Asn], positioned in a cis pattern, as plausible pathogenic contributors to early-onset hearing loss characterized by a severe and progressive course. Moreover, bioinformatics analysis showd disruptin in hydrogen bonding of mutant amino acids with interactive amino acids. Conclusion: Our research uncovered a relationship between mutations in the MYO6 gene and non-syndromic hearing loss. We identified two variants, c.[2377T>G; 2382G>T] p.[Trp793Gly; Lys794Asn] in MYO6 as strong candidates responsible for the observed progressive hereditary hearing loss. This study not only adds to our knowledge about hearing problems related to MYO6 but also reveals the presence of monogenic compound heterozygosity. Our study will provide a new sight for genetic diagnosis in such patients and their management for future use.
摘要：
背景：MYO6基因突变与常染色体显性遗传非综合征性听力损失（ADNSHL）和常染色体隐性遗传非综合征性听力损失（ARNSHL）有关，累积鉴定125个致病变异。为了调查患有遗传性听力损失的中国家庭中的潜在遗传因素，促进了高通量测序的利用。方法：进行详细的临床调查。基因检测是通过使用目标组测序进行的，还有Sanger测序.靶向测序鉴定了变体,并且采用Sanger测序来验证家族内鉴定的变体的分离。此外,我们进行了生物信息学分析以加强我们的发现.结果：临床调查显示，家庭成员受到进行性和感觉神经性听力损失的影响，发病在8-10岁左右。此外，基因检测发现了新的MYO6变异，c.[2377T>G；2382G>T]p.[Trp793Gly；Lys794Asn]，以顺式模式定位，作为以严重和进行性病程为特征的早发性听力损失的合理致病因素。此外，生物信息学分析显示，突变氨基酸与氨基酸相互作用的氢键结合。结论：我们的研究揭示了MYO6基因突变与非综合征性听力损失之间的关系。我们确定了两个变异体,c.MYO6中的[2377T>G;2382G>T]p.[Trp793Gly;Lys794Asn]是导致观察到的进行性遗传性听力损失的有力候选者。这项研究不仅增加了我们对与MYO6相关的听力问题的了解，而且还揭示了单基因复合杂合性的存在。我们的研究将为此类患者的遗传诊断及其未来使用的管理提供新的视野。
