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Exome Sequencing Identifies a Novel CEACAM16 Mutation Associated with Autosomal Dominant Nonsyndromic Hearing Loss DFNA4B in a Chinese Family
Autosomal dominant nonsyndromic hearing loss (ADNSHL/DFNA) is a highly genetically heterogeneous disorder. Hitherto only about 30 ADNSHL-causing genes have been identified and many unknown genes remain to be discovered. In this research, genome-wide linkage analysis mapped the disease locus to a 4.3...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375019/ https://www.ncbi.nlm.nih.gov/pubmed/25589040 http://dx.doi.org/10.1038/jhg.2014.114 |
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author | Wang, Honghan Wang, Xinwei He, Chufeng Li, Haibo Qing, Jie Grati, Mhamed Hu, Zhengmao Li, Jiada Hu, Yiqiao Xia, Kun Mei, Lingyun Wang, Xingwei Yu, Jianjun Chen, Hongsheng Jiang, Lu Liu, Yalan Men, Meichao Zhang, Hailin Guan, Liping Xiao, Jingjing Zhang, Jianguo Liu, Xuezhong Feng, Yong |
author_facet | Wang, Honghan Wang, Xinwei He, Chufeng Li, Haibo Qing, Jie Grati, Mhamed Hu, Zhengmao Li, Jiada Hu, Yiqiao Xia, Kun Mei, Lingyun Wang, Xingwei Yu, Jianjun Chen, Hongsheng Jiang, Lu Liu, Yalan Men, Meichao Zhang, Hailin Guan, Liping Xiao, Jingjing Zhang, Jianguo Liu, Xuezhong Feng, Yong |
author_sort | Wang, Honghan |
collection | PubMed |
description | Autosomal dominant nonsyndromic hearing loss (ADNSHL/DFNA) is a highly genetically heterogeneous disorder. Hitherto only about 30 ADNSHL-causing genes have been identified and many unknown genes remain to be discovered. In this research, genome-wide linkage analysis mapped the disease locus to a 4.3 Mb region on chromosome 19q13 in SY-026, a five-generation nonconsanguineous Chinese family affected by late-onset and progressive ADNSHL. This linkage region showed partial overlap with the previously reported DFNA4. Simultaneously, probands were analyzed using exome capture followed by next generation sequencing. Encouragingly, a heterozygous missense mutation, c.505G>A (p.G169R) in exon 3 of the CEACAM16 gene (carcinoembryonic antigen-related cell adhesion molecule 16), was identified via this combined strategy. Sanger sequencing verified that the mutation co-segregated with hearing loss in the family and that it was not present in 200 unrelated control subjects with matched ancestry. This is the second report in the literature of a family with ADNSHL caused by CEACAM16 mutation. Immunofluorescence staining and Western blots also prove CEACAM16 to be a secreted protein. Furthermore, our studies in transfected HEK293T cells show that the secretion efficacy of the mutant CEACAM16 is much lower than that of the wild-type, suggesting a deleterious effect of the sequence variant. |
format | Online Article Text |
id | pubmed-4375019 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-43750192015-09-01 Exome Sequencing Identifies a Novel CEACAM16 Mutation Associated with Autosomal Dominant Nonsyndromic Hearing Loss DFNA4B in a Chinese Family Wang, Honghan Wang, Xinwei He, Chufeng Li, Haibo Qing, Jie Grati, Mhamed Hu, Zhengmao Li, Jiada Hu, Yiqiao Xia, Kun Mei, Lingyun Wang, Xingwei Yu, Jianjun Chen, Hongsheng Jiang, Lu Liu, Yalan Men, Meichao Zhang, Hailin Guan, Liping Xiao, Jingjing Zhang, Jianguo Liu, Xuezhong Feng, Yong J Hum Genet Article Autosomal dominant nonsyndromic hearing loss (ADNSHL/DFNA) is a highly genetically heterogeneous disorder. Hitherto only about 30 ADNSHL-causing genes have been identified and many unknown genes remain to be discovered. In this research, genome-wide linkage analysis mapped the disease locus to a 4.3 Mb region on chromosome 19q13 in SY-026, a five-generation nonconsanguineous Chinese family affected by late-onset and progressive ADNSHL. This linkage region showed partial overlap with the previously reported DFNA4. Simultaneously, probands were analyzed using exome capture followed by next generation sequencing. Encouragingly, a heterozygous missense mutation, c.505G>A (p.G169R) in exon 3 of the CEACAM16 gene (carcinoembryonic antigen-related cell adhesion molecule 16), was identified via this combined strategy. Sanger sequencing verified that the mutation co-segregated with hearing loss in the family and that it was not present in 200 unrelated control subjects with matched ancestry. This is the second report in the literature of a family with ADNSHL caused by CEACAM16 mutation. Immunofluorescence staining and Western blots also prove CEACAM16 to be a secreted protein. Furthermore, our studies in transfected HEK293T cells show that the secretion efficacy of the mutant CEACAM16 is much lower than that of the wild-type, suggesting a deleterious effect of the sequence variant. 2015-01-15 2015-03 /pmc/articles/PMC4375019/ /pubmed/25589040 http://dx.doi.org/10.1038/jhg.2014.114 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Wang, Honghan Wang, Xinwei He, Chufeng Li, Haibo Qing, Jie Grati, Mhamed Hu, Zhengmao Li, Jiada Hu, Yiqiao Xia, Kun Mei, Lingyun Wang, Xingwei Yu, Jianjun Chen, Hongsheng Jiang, Lu Liu, Yalan Men, Meichao Zhang, Hailin Guan, Liping Xiao, Jingjing Zhang, Jianguo Liu, Xuezhong Feng, Yong Exome Sequencing Identifies a Novel CEACAM16 Mutation Associated with Autosomal Dominant Nonsyndromic Hearing Loss DFNA4B in a Chinese Family |
title | Exome Sequencing Identifies a Novel CEACAM16 Mutation Associated with Autosomal Dominant Nonsyndromic Hearing Loss DFNA4B in a Chinese Family |
title_full | Exome Sequencing Identifies a Novel CEACAM16 Mutation Associated with Autosomal Dominant Nonsyndromic Hearing Loss DFNA4B in a Chinese Family |
title_fullStr | Exome Sequencing Identifies a Novel CEACAM16 Mutation Associated with Autosomal Dominant Nonsyndromic Hearing Loss DFNA4B in a Chinese Family |
title_full_unstemmed | Exome Sequencing Identifies a Novel CEACAM16 Mutation Associated with Autosomal Dominant Nonsyndromic Hearing Loss DFNA4B in a Chinese Family |
title_short | Exome Sequencing Identifies a Novel CEACAM16 Mutation Associated with Autosomal Dominant Nonsyndromic Hearing Loss DFNA4B in a Chinese Family |
title_sort | exome sequencing identifies a novel ceacam16 mutation associated with autosomal dominant nonsyndromic hearing loss dfna4b in a chinese family |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375019/ https://www.ncbi.nlm.nih.gov/pubmed/25589040 http://dx.doi.org/10.1038/jhg.2014.114 |
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