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SIX2 haploinsufficiency causes conductive hearing loss with ptosis in humans

The ossicles represent one of the most fundamental morphological features in evolutionary biology of the mammalians. The mobile ossicular morphology abnormalities result in the severe conductive hearing loss. Development and patterning of the middle ear malformation depend on genetic and environment...

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Autores principales: Guan, Jing, Wang, Dayong, Cao, Wenjian, Zhao, Yali, Du, Renqian, Yuan, Hu, Liu, Qiong, Lan, Lan, Zong, Liang, Yang, Ju, Yin, Zifang, Han, Bing, Zhang, Feng, Wang, Qiuju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411491/
https://www.ncbi.nlm.nih.gov/pubmed/27383657
http://dx.doi.org/10.1038/jhg.2016.86
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author Guan, Jing
Wang, Dayong
Cao, Wenjian
Zhao, Yali
Du, Renqian
Yuan, Hu
Liu, Qiong
Lan, Lan
Zong, Liang
Yang, Ju
Yin, Zifang
Han, Bing
Zhang, Feng
Wang, Qiuju
author_facet Guan, Jing
Wang, Dayong
Cao, Wenjian
Zhao, Yali
Du, Renqian
Yuan, Hu
Liu, Qiong
Lan, Lan
Zong, Liang
Yang, Ju
Yin, Zifang
Han, Bing
Zhang, Feng
Wang, Qiuju
author_sort Guan, Jing
collection PubMed
description The ossicles represent one of the most fundamental morphological features in evolutionary biology of the mammalians. The mobile ossicular morphology abnormalities result in the severe conductive hearing loss. Development and patterning of the middle ear malformation depend on genetic and environmental causes. However, the genetic basis for the risk of congenital ossicle malformation is poorly understood. We show here nine affected individuals in a Chinese pedigree who had bilateral conductive hearing loss with ptosis. We performed whole-genome sequencing and array comparative genomic hybridization (CGH) analysis on DNA samples from the Chinese pedigree. We confirmed the presence of a novel 60 kb heterozygous deletion in size, encompassing SIX2 in our family. Mutation screening in 169 sporadic cases with external ear and middle ear malformations identified no pathogenic variant or polymorphism. We suggest SIX2 haploinsufficiency as a potential congenital factor could be attributed to developmental malformation of the middle ear ossicles and upper eyelid. To the best of our knowledge, this is the first report to provide a description of copy number variation in the SIX2 gene resulting in syndromic conductive hearing loss.
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spelling pubmed-54114912017-05-15 SIX2 haploinsufficiency causes conductive hearing loss with ptosis in humans Guan, Jing Wang, Dayong Cao, Wenjian Zhao, Yali Du, Renqian Yuan, Hu Liu, Qiong Lan, Lan Zong, Liang Yang, Ju Yin, Zifang Han, Bing Zhang, Feng Wang, Qiuju J Hum Genet Original Article The ossicles represent one of the most fundamental morphological features in evolutionary biology of the mammalians. The mobile ossicular morphology abnormalities result in the severe conductive hearing loss. Development and patterning of the middle ear malformation depend on genetic and environmental causes. However, the genetic basis for the risk of congenital ossicle malformation is poorly understood. We show here nine affected individuals in a Chinese pedigree who had bilateral conductive hearing loss with ptosis. We performed whole-genome sequencing and array comparative genomic hybridization (CGH) analysis on DNA samples from the Chinese pedigree. We confirmed the presence of a novel 60 kb heterozygous deletion in size, encompassing SIX2 in our family. Mutation screening in 169 sporadic cases with external ear and middle ear malformations identified no pathogenic variant or polymorphism. We suggest SIX2 haploinsufficiency as a potential congenital factor could be attributed to developmental malformation of the middle ear ossicles and upper eyelid. To the best of our knowledge, this is the first report to provide a description of copy number variation in the SIX2 gene resulting in syndromic conductive hearing loss. Nature Publishing Group 2016-11 2016-07-07 /pmc/articles/PMC5411491/ /pubmed/27383657 http://dx.doi.org/10.1038/jhg.2016.86 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original Article
Guan, Jing
Wang, Dayong
Cao, Wenjian
Zhao, Yali
Du, Renqian
Yuan, Hu
Liu, Qiong
Lan, Lan
Zong, Liang
Yang, Ju
Yin, Zifang
Han, Bing
Zhang, Feng
Wang, Qiuju
SIX2 haploinsufficiency causes conductive hearing loss with ptosis in humans
title SIX2 haploinsufficiency causes conductive hearing loss with ptosis in humans
title_full SIX2 haploinsufficiency causes conductive hearing loss with ptosis in humans
title_fullStr SIX2 haploinsufficiency causes conductive hearing loss with ptosis in humans
title_full_unstemmed SIX2 haploinsufficiency causes conductive hearing loss with ptosis in humans
title_short SIX2 haploinsufficiency causes conductive hearing loss with ptosis in humans
title_sort six2 haploinsufficiency causes conductive hearing loss with ptosis in humans
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411491/
https://www.ncbi.nlm.nih.gov/pubmed/27383657
http://dx.doi.org/10.1038/jhg.2016.86
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