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Two Compound Heterozygous Were Identified in SLC26A4 Gene in Two Chinese Families With Enlarged Vestibular Aqueduct

OBJECTIVES: To investigate the genetic causes of hearing loss with enlarged vestibular aqueduct (EVA) in two children from unrelated two Chinese families. METHODS: Sanger sequencing of all coding exons in SLC26A4 (encoding Pendrin protein) was performed on the two patients, their sibling and parents...

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Autores principales: Yu, Yongbo, Yang, Yang, Lu, Jie, Jin, Yaqiong, Yang, Yeran, Hong, Enyu, Shi, Jin, Chen, Feng, Han, Shujing, Chu, Ping, Guo, Yongli, Ni, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society of Otorhinolaryngology-Head and Neck Surgery 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315218/
https://www.ncbi.nlm.nih.gov/pubmed/30086623
http://dx.doi.org/10.21053/ceo.2018.00213
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author Yu, Yongbo
Yang, Yang
Lu, Jie
Jin, Yaqiong
Yang, Yeran
Hong, Enyu
Shi, Jin
Chen, Feng
Han, Shujing
Chu, Ping
Guo, Yongli
Ni, Xin
author_facet Yu, Yongbo
Yang, Yang
Lu, Jie
Jin, Yaqiong
Yang, Yeran
Hong, Enyu
Shi, Jin
Chen, Feng
Han, Shujing
Chu, Ping
Guo, Yongli
Ni, Xin
author_sort Yu, Yongbo
collection PubMed
description OBJECTIVES: To investigate the genetic causes of hearing loss with enlarged vestibular aqueduct (EVA) in two children from unrelated two Chinese families. METHODS: Sanger sequencing of all coding exons in SLC26A4 (encoding Pendrin protein) was performed on the two patients, their sibling and parents respectively. To predict and visualize the potential functional outcome of the novel variant, model building, structure analysis, and in silico analysis were further conducted. RESULTS: The results showed that the proband from family I harbored a compound heterozygote of SLC26A4 c.1174A>T (p.N392Y) mutation and c.1181delTCT (p.F394del) variant in exon 10, potentially altering Pendrin protein structure. In family II, the proband was identified in compound heterozygosity with a known mutation of c.919-2A>G in the splice site of intron 7 and a novel mutation of c.1023insC in exon 9, which results in a frameshift and translational termination, consequently leading to truncated Pendrin protein. Sequence homology analysis indicated that all the mutations localized at high conservation sites, which emphasized the significance of these mutations on Pendrin spatial organization and function. CONCLUSION: In summary, this study revealed two compound heterozygous mutations (c.1174A>T/c.1181delTCT; c.919- 2A>G/c.1023insC) in Pendrin protein, which might account for the deafness of the two probands clinically diagnosed with EVA. Thus this study contributes to improve understanding of the causes of hearing loss associated with EVA and develop a more scientific screening strategy for deafness.
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spelling pubmed-63152182019-02-01 Two Compound Heterozygous Were Identified in SLC26A4 Gene in Two Chinese Families With Enlarged Vestibular Aqueduct Yu, Yongbo Yang, Yang Lu, Jie Jin, Yaqiong Yang, Yeran Hong, Enyu Shi, Jin Chen, Feng Han, Shujing Chu, Ping Guo, Yongli Ni, Xin Clin Exp Otorhinolaryngol Original Article OBJECTIVES: To investigate the genetic causes of hearing loss with enlarged vestibular aqueduct (EVA) in two children from unrelated two Chinese families. METHODS: Sanger sequencing of all coding exons in SLC26A4 (encoding Pendrin protein) was performed on the two patients, their sibling and parents respectively. To predict and visualize the potential functional outcome of the novel variant, model building, structure analysis, and in silico analysis were further conducted. RESULTS: The results showed that the proband from family I harbored a compound heterozygote of SLC26A4 c.1174A>T (p.N392Y) mutation and c.1181delTCT (p.F394del) variant in exon 10, potentially altering Pendrin protein structure. In family II, the proband was identified in compound heterozygosity with a known mutation of c.919-2A>G in the splice site of intron 7 and a novel mutation of c.1023insC in exon 9, which results in a frameshift and translational termination, consequently leading to truncated Pendrin protein. Sequence homology analysis indicated that all the mutations localized at high conservation sites, which emphasized the significance of these mutations on Pendrin spatial organization and function. CONCLUSION: In summary, this study revealed two compound heterozygous mutations (c.1174A>T/c.1181delTCT; c.919- 2A>G/c.1023insC) in Pendrin protein, which might account for the deafness of the two probands clinically diagnosed with EVA. Thus this study contributes to improve understanding of the causes of hearing loss associated with EVA and develop a more scientific screening strategy for deafness. Korean Society of Otorhinolaryngology-Head and Neck Surgery 2019-02 2018-08-09 /pmc/articles/PMC6315218/ /pubmed/30086623 http://dx.doi.org/10.21053/ceo.2018.00213 Text en Copyright © 2019 by Korean Society of Otorhinolaryngology-Head and Neck Surgery This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Yu, Yongbo
Yang, Yang
Lu, Jie
Jin, Yaqiong
Yang, Yeran
Hong, Enyu
Shi, Jin
Chen, Feng
Han, Shujing
Chu, Ping
Guo, Yongli
Ni, Xin
Two Compound Heterozygous Were Identified in SLC26A4 Gene in Two Chinese Families With Enlarged Vestibular Aqueduct
title Two Compound Heterozygous Were Identified in SLC26A4 Gene in Two Chinese Families With Enlarged Vestibular Aqueduct
title_full Two Compound Heterozygous Were Identified in SLC26A4 Gene in Two Chinese Families With Enlarged Vestibular Aqueduct
title_fullStr Two Compound Heterozygous Were Identified in SLC26A4 Gene in Two Chinese Families With Enlarged Vestibular Aqueduct
title_full_unstemmed Two Compound Heterozygous Were Identified in SLC26A4 Gene in Two Chinese Families With Enlarged Vestibular Aqueduct
title_short Two Compound Heterozygous Were Identified in SLC26A4 Gene in Two Chinese Families With Enlarged Vestibular Aqueduct
title_sort two compound heterozygous were identified in slc26a4 gene in two chinese families with enlarged vestibular aqueduct
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315218/
https://www.ncbi.nlm.nih.gov/pubmed/30086623
http://dx.doi.org/10.21053/ceo.2018.00213
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