A non-coding variant in 5' untranslated region drove up-regulation of pseudo-kinase EPHA10 and caused non-syndromic hearing loss in humans. Issue 5 (1st September 2022)

• Record Type: Journal Article
• Authors: Huang, Sida; Ma, Lu; Liu, Xuezhong; He, Chufeng; Li, Jiada; Hu, Zhengmao; Jiang, Lu; Liu, Yalan; Liu, Xianlin; Feng, Yong; Cai, Xinzhang
• Is Part Of: Human molecular genetics. Volume 32:Issue 5(2023)
• Page Start: 720
• Page End: 731
• Publication Date: 2022-09-01
• Subjects: Human molecular genetics -- Periodicals; Human chromosome abnormalities -- Periodicals; 572.8
• DOI: 10.1093/hmg/ddac223
• Languages: English
• ISSNs: 0964-6906

Abstract

Abstract: Hereditary hearing loss has a genetic and phenotypic heterogeneity. However, it is still difficult to explain this heterogeneity perfectly with known deafness genes. Here, we report a novel causative gene EPHA10 as well as its non-coding variant in 5′ untranslated region identified in a family with post-lingual autosomal dominant non-syndromic hearing loss from southern China. One affected member of this family had an ideal hearing restoration after cochlear implantation. We speculated that there were probable deafness-causing abnormalities in the cochlea according to clinical imaging and auditory evaluations. A heterozygous variant c.-81_-73delinsAGC was found co-segregating with hearing loss. Epha10 was expressed in mouse cochlea at both transcription and translation levels. The variant caused upregulation of EPHA10 which may result from promoter activity enhancement after sequence change. Overexpression of Eph (the homolog of human EPHA10) exerted effects on the structure and function of chordotonal organ in fly model. In summary, our study linked pseudo-kinase EPHA10 to hearing loss in humans for the first time. Graphical Abstract: