Jin Aixia, Zhao Qingqing, Liu Shuting, Jin Zi-Bing, Li Shuyan, Xiang Mengqing, Zeng Mingbing, Jin Kangxin
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, China.
Front Cell Dev Biol. 2022 Apr 21;10:794837. doi: 10.3389/fcell.2022.794837. eCollection 2022.
Congenital hereditary cataract is genetically heterogeneous and the leading cause of visual impairment in children. Identification of hereditary causes is critical to genetic counselling and family planning. Here, we examined a four-generation Chinese pedigree with congenital dominant cataract and identified a new mutation in via targeted exome sequencing. A heterozygous missense mutation c.263C > T, leading to a proline-to-Leucine conversion at the conserved residue 88 in the second transmembrane domain of human connexin 50 (Cx50), was identified in all patients but not in unaffected family members. Functional analyses of the mutation revealed that it disrupted the stability of Cx50 and had a deleterious effect on protein function. Indeed, the mutation compromised normal membrane permeability and gating of ions, and impeded cell migration when overexpressed. Together, our results expand the pathogenic mutation spectrum of Cx50 underlying congenital cataract and lend more support to clinical diagnosis and genetic counseling.
先天性遗传性白内障具有遗传异质性，是儿童视力障碍的主要原因。确定遗传病因对于遗传咨询和计划生育至关重要。在此，我们研究了一个患有先天性显性白内障的四代中国家系，并通过靶向外显子组测序在其中鉴定出一个新的突变。在所有患者中均鉴定出一个杂合错义突变c.263C>T，该突变导致人类连接蛋白50（Cx50）第二个跨膜结构域中保守残基88处的脯氨酸转换为亮氨酸，而未患病的家庭成员中未发现该突变。对该突变的功能分析表明，它破坏了Cx50的稳定性，并对蛋白质功能产生有害影响。实际上，该突变损害了正常的膜通透性和离子门控，并且在过表达时会阻碍细胞迁移。总之，我们的结果扩展了先天性白内障潜在的Cx50致病突变谱，并为临床诊断和遗传咨询提供了更多支持。
