文献类型：期刊文献

英文题名：Case Report: A Novel GJB2 Missense Variant Inherited From the Low-Level Mosaic Mother in a Chinese Female With Palmoplantar Keratoderma With Deafness

作者：Tian, Xinyuan[1,2];Zhang, Chuan[2];Zhou, Bingbo[2];Chen, Xue[2];Feng, Xuan[2];Zheng, Lei[2];Wang, Yupei[2];Hao, Shengju[2];Hui, Ling[2]

第一作者：Tian, Xinyuan;田小雨

通信作者：Hui, L[1]

机构：[1]Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou, Peoples R China;[2]Gansu Prov Matern & Child Hlth Hosp, Ctr Med Genet, Gansu Prov Clin Res Ctr Birth Defects & Rare Dis, Lanzhou, Peoples R China

第一机构：甘肃中医药大学公共卫生学院

通信机构：[1]corresponding author), Gansu Prov Matern & Child Hlth Hosp, Ctr Med Genet, Gansu Prov Clin Res Ctr Birth Defects & Rare Dis, Lanzhou, Peoples R China.

年份：2022

卷号：13

外文期刊名：FRONTIERS IN GENETICS

收录：;Scopus(收录号：2-s2.0-85135493883);WOS:【SCI-EXPANDED(收录号:WOS:000837077600001)】；

基金：Funding This work was supported by the Science and Technology Program of Gansu Province (21JR7RA680) and the National Natural Science Foundation of China (1200051339).

语种：英文

外文关键词：GJB2 gene; palmoplantar keratoderma; hearing loss; dominant variant; mosaicism

摘要：Dominant variants in the gap junction beta-2 (GJB2) gene may lead to various degrees of syndromic hearing loss (SHL) which is manifest as sensorineural hearing impairment and hyperproliferative epidermal disorders, including palmoplantar keratoderma with deafness (PPKDFN). So far, only a few GJB2 dominant variants causing PPKDFN have been discovered. Through the whole-exome sequencing (WES), a Chinese female patient with severe palmoplantar hyperkeratosis and delayed-onset hearing loss has been identified. She had a novel heterozygous variant, c.224G>C (p.R75P), in the GJB2 gene, which was unreported previously. The proband's mother who had a mild phenotype was suggested the possibility of mosaicism by WES (similar to 120x), and the ultra-deep targeted sequencing (similar to 20,000x) was used for detecting low-level mosaic variants which provided accurate recurrence-risk estimates and genetic counseling. In addition, the analysis of protein structure indicated that the structural stability and permeability of the connexin 26 (Cx26) gap junction channel may be disrupted by the p.R75P variant. Through retrospective analysis, it is detected that the junction of extracellular region-1 (EC1) and transmembrane region-2 (TM2) is a variant hotspot for PPKDFN, such as p.R75. Our report reflects the important and effective diagnostic role of WES in PPKDFN and low-level mosaicism, expands the spectrum of the GJB2 variant, and furthermore provides strong proof about the relevance between the p.R75P variant in GJB2 and PPKDFN.