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Due to its high genetic and clinical heterogeneity, the identification of ADCC-associated gene mutations is essential for the development of molecular therapies. In this study, we examined a four-generation Chinese pedigree with ADCC and identified putative mutations in ADCC candidate genes via next-generation sequencing (NGS) followed by Sanger sequencing. A novel missense mutation in <jats:italic>GJA8<\/jats:italic> (c.T217C) in ADCC patients causes a serine-to-proline substitution at residue 73 of connexin 50 (Cx50); no mutation was found in unaffected family members and unrelated healthy individuals. Functional analysis revealed that this missense mutation disrupts protein function in human lens epithelial cells (HLEpiCs), which fails to form calcium-sensitive hemichannels. Furthermore, mutant Cx50 leads to decreased ROS scavenging by inhibiting <jats:italic>G6PD<\/jats:italic> expression and thus induces cell apoptosis via aberrant activation of the unfolded protein response (UPR). In conclusion, we report a novel <jats:italic>GJA8<\/jats:italic> heterozygous mutation in a Chinese family with a vital role in ADCC, broadening the genetic spectrum of this disease.<\/jats:p>","DOI":"10.1038\/s41598-019-55549-1","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T11:03:32Z","timestamp":1576494212000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["GJA8 missense mutation disrupts hemichannels and induces cell apoptosis in human lens epithelial cells"],"prefix":"10.1038","volume":"9","author":[{"given":"Li","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da-Bei","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Ting","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi-Bing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang-Ying","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,16]]},"reference":[{"key":"55549_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/srep28564","volume":"6","author":"X Wu","year":"2016","unstructured":"Wu, X., Long, E., Lin, H. & Liu, Y. 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