Cargando…
Case Report: A Novel GJB2 Missense Variant Inherited From the Low-Level Mosaic Mother in a Chinese Female With Palmoplantar Keratoderma With Deafness
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 do...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354265/ https://www.ncbi.nlm.nih.gov/pubmed/35938034 http://dx.doi.org/10.3389/fgene.2022.938639 |
_version_ | 1784763028871315456 |
---|---|
author | Tian, Xinyuan Zhang, Chuan Zhou, Bingbo Chen, Xue Feng, Xuan Zheng, Lei Wang, Yupei Hao, Shengju Hui, Ling |
author_facet | Tian, Xinyuan Zhang, Chuan Zhou, Bingbo Chen, Xue Feng, Xuan Zheng, Lei Wang, Yupei Hao, Shengju Hui, Ling |
author_sort | Tian, Xinyuan |
collection | PubMed |
description | 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 (∼120×), and the ultra-deep targeted sequencing (∼20,000×) 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. |
format | Online Article Text |
id | pubmed-9354265 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93542652022-08-06 Case Report: A Novel GJB2 Missense Variant Inherited From the Low-Level Mosaic Mother in a Chinese Female With Palmoplantar Keratoderma With Deafness Tian, Xinyuan Zhang, Chuan Zhou, Bingbo Chen, Xue Feng, Xuan Zheng, Lei Wang, Yupei Hao, Shengju Hui, Ling Front Genet Genetics 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 (∼120×), and the ultra-deep targeted sequencing (∼20,000×) 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. Frontiers Media S.A. 2022-07-22 /pmc/articles/PMC9354265/ /pubmed/35938034 http://dx.doi.org/10.3389/fgene.2022.938639 Text en Copyright © 2022 Tian, Zhang, Zhou, Chen, Feng, Zheng, Wang, Hao and Hui. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Tian, Xinyuan Zhang, Chuan Zhou, Bingbo Chen, Xue Feng, Xuan Zheng, Lei Wang, Yupei Hao, Shengju Hui, Ling Case Report: A Novel GJB2 Missense Variant Inherited From the Low-Level Mosaic Mother in a Chinese Female With Palmoplantar Keratoderma With Deafness |
title | Case Report: A Novel GJB2 Missense Variant Inherited From the Low-Level Mosaic Mother in a Chinese Female With Palmoplantar Keratoderma With Deafness |
title_full | Case Report: A Novel GJB2 Missense Variant Inherited From the Low-Level Mosaic Mother in a Chinese Female With Palmoplantar Keratoderma With Deafness |
title_fullStr | Case Report: A Novel GJB2 Missense Variant Inherited From the Low-Level Mosaic Mother in a Chinese Female With Palmoplantar Keratoderma With Deafness |
title_full_unstemmed | Case Report: A Novel GJB2 Missense Variant Inherited From the Low-Level Mosaic Mother in a Chinese Female With Palmoplantar Keratoderma With Deafness |
title_short | Case Report: A Novel GJB2 Missense Variant Inherited From the Low-Level Mosaic Mother in a Chinese Female With Palmoplantar Keratoderma With Deafness |
title_sort | case report: a novel gjb2 missense variant inherited from the low-level mosaic mother in a chinese female with palmoplantar keratoderma with deafness |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354265/ https://www.ncbi.nlm.nih.gov/pubmed/35938034 http://dx.doi.org/10.3389/fgene.2022.938639 |
work_keys_str_mv | AT tianxinyuan casereportanovelgjb2missensevariantinheritedfromthelowlevelmosaicmotherinachinesefemalewithpalmoplantarkeratodermawithdeafness AT zhangchuan casereportanovelgjb2missensevariantinheritedfromthelowlevelmosaicmotherinachinesefemalewithpalmoplantarkeratodermawithdeafness AT zhoubingbo casereportanovelgjb2missensevariantinheritedfromthelowlevelmosaicmotherinachinesefemalewithpalmoplantarkeratodermawithdeafness AT chenxue casereportanovelgjb2missensevariantinheritedfromthelowlevelmosaicmotherinachinesefemalewithpalmoplantarkeratodermawithdeafness AT fengxuan casereportanovelgjb2missensevariantinheritedfromthelowlevelmosaicmotherinachinesefemalewithpalmoplantarkeratodermawithdeafness AT zhenglei casereportanovelgjb2missensevariantinheritedfromthelowlevelmosaicmotherinachinesefemalewithpalmoplantarkeratodermawithdeafness AT wangyupei casereportanovelgjb2missensevariantinheritedfromthelowlevelmosaicmotherinachinesefemalewithpalmoplantarkeratodermawithdeafness AT haoshengju casereportanovelgjb2missensevariantinheritedfromthelowlevelmosaicmotherinachinesefemalewithpalmoplantarkeratodermawithdeafness AT huiling casereportanovelgjb2missensevariantinheritedfromthelowlevelmosaicmotherinachinesefemalewithpalmoplantarkeratodermawithdeafness |