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Waardenburg syndrome type II in a Chinese pedigree caused by frameshift mutation in the SOX10 gene

Waardenburg syndrome (WS) is a congenital hereditary disease, attributed to the most common symptoms of sensorineural deafness and iris hypopigmentation. It is also known as the hearing-pigmentation deficient syndrome. Mutations on SOXl0 gene often lead to congenital deafness and has been shown to p...

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Autores principales: Li, Li, Ma, Jing, He, Xiao-li, Zhou, Yuan-tao, Zhang, Yu, Chen, Quan-dong, Zhang, Lin, Ruan, Biao, Zhang, Tie-Song
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217986/
https://www.ncbi.nlm.nih.gov/pubmed/33345266
http://dx.doi.org/10.1042/BSR20193375
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author Li, Li
Ma, Jing
He, Xiao-li
Zhou, Yuan-tao
Zhang, Yu
Chen, Quan-dong
Zhang, Lin
Ruan, Biao
Zhang, Tie-Song
author_facet Li, Li
Ma, Jing
He, Xiao-li
Zhou, Yuan-tao
Zhang, Yu
Chen, Quan-dong
Zhang, Lin
Ruan, Biao
Zhang, Tie-Song
author_sort Li, Li
collection PubMed
description Waardenburg syndrome (WS) is a congenital hereditary disease, attributed to the most common symptoms of sensorineural deafness and iris hypopigmentation. It is also known as the hearing-pigmentation deficient syndrome. Mutations on SOXl0 gene often lead to congenital deafness and has been shown to play an important role in the pathogenesis of WS. We investigated one family of five members, with four patients exhibiting the classic form of WS2, whose DNA samples were analyzed by the technique of Whole-exome sequencing (WES). From analysis of WES data, we found that both the mother and all three children in the family have a heterozygous mutation on the Sex Determining Region Y - Box 10 (SOX10) gene. The mutation was c.298_300delinsGG in exon 2 of SOX10 (NM_006941), which leads to a frameshift of nine nucleotides, hence the amino acids (p. S100Rfs*9) are altered and the protein translation may be terminated prematurely. Further flow cytometry confirmed significant down-regulation of SOX10 protein, which indicated the SOX10 gene mutation was responsible for the pathogenesis of WS2 patients. In addition, we speculated that some other mutated genes might be related to disease phenotype in this family, which might also participate in promoting the progression of WS2.
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spelling pubmed-82179862021-07-02 Waardenburg syndrome type II in a Chinese pedigree caused by frameshift mutation in the SOX10 gene Li, Li Ma, Jing He, Xiao-li Zhou, Yuan-tao Zhang, Yu Chen, Quan-dong Zhang, Lin Ruan, Biao Zhang, Tie-Song Biosci Rep Gene Expression & Regulation Waardenburg syndrome (WS) is a congenital hereditary disease, attributed to the most common symptoms of sensorineural deafness and iris hypopigmentation. It is also known as the hearing-pigmentation deficient syndrome. Mutations on SOXl0 gene often lead to congenital deafness and has been shown to play an important role in the pathogenesis of WS. We investigated one family of five members, with four patients exhibiting the classic form of WS2, whose DNA samples were analyzed by the technique of Whole-exome sequencing (WES). From analysis of WES data, we found that both the mother and all three children in the family have a heterozygous mutation on the Sex Determining Region Y - Box 10 (SOX10) gene. The mutation was c.298_300delinsGG in exon 2 of SOX10 (NM_006941), which leads to a frameshift of nine nucleotides, hence the amino acids (p. S100Rfs*9) are altered and the protein translation may be terminated prematurely. Further flow cytometry confirmed significant down-regulation of SOX10 protein, which indicated the SOX10 gene mutation was responsible for the pathogenesis of WS2 patients. In addition, we speculated that some other mutated genes might be related to disease phenotype in this family, which might also participate in promoting the progression of WS2. Portland Press Ltd. 2021-06-18 /pmc/articles/PMC8217986/ /pubmed/33345266 http://dx.doi.org/10.1042/BSR20193375 Text en © 2020 The Author(s). https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Gene Expression & Regulation
Li, Li
Ma, Jing
He, Xiao-li
Zhou, Yuan-tao
Zhang, Yu
Chen, Quan-dong
Zhang, Lin
Ruan, Biao
Zhang, Tie-Song
Waardenburg syndrome type II in a Chinese pedigree caused by frameshift mutation in the SOX10 gene
title Waardenburg syndrome type II in a Chinese pedigree caused by frameshift mutation in the SOX10 gene
title_full Waardenburg syndrome type II in a Chinese pedigree caused by frameshift mutation in the SOX10 gene
title_fullStr Waardenburg syndrome type II in a Chinese pedigree caused by frameshift mutation in the SOX10 gene
title_full_unstemmed Waardenburg syndrome type II in a Chinese pedigree caused by frameshift mutation in the SOX10 gene
title_short Waardenburg syndrome type II in a Chinese pedigree caused by frameshift mutation in the SOX10 gene
title_sort waardenburg syndrome type ii in a chinese pedigree caused by frameshift mutation in the sox10 gene
topic Gene Expression & Regulation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217986/
https://www.ncbi.nlm.nih.gov/pubmed/33345266
http://dx.doi.org/10.1042/BSR20193375
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