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Resolving the genetic heterogeneity of prelingual hearing loss within one family: Performance comparison and application of two targeted next generation sequencing approaches
Here, we report an unconventional Chinese pedigree consisting of three branches all segregating prelingual hearing loss (HL) with unclear inheritance pattern. After identifying the cause of one branch as maternally inherited aminoglycoside-induced HL, targeted next generation sequencing (NGS) was ap...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521291/ https://www.ncbi.nlm.nih.gov/pubmed/25231367 http://dx.doi.org/10.1038/jhg.2014.78 |
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author | Lu, Yu Zhou, Xueya Jin, Zhanguo Cheng, Jing Shen, Weidong Ji, Fei Liu, Liyang Zhang, Xuegong Zhang, Michael Cao, Ye Han, Dongyi Choy, KwongWai Yuan, Huijun |
author_facet | Lu, Yu Zhou, Xueya Jin, Zhanguo Cheng, Jing Shen, Weidong Ji, Fei Liu, Liyang Zhang, Xuegong Zhang, Michael Cao, Ye Han, Dongyi Choy, KwongWai Yuan, Huijun |
author_sort | Lu, Yu |
collection | PubMed |
description | Here, we report an unconventional Chinese pedigree consisting of three branches all segregating prelingual hearing loss (HL) with unclear inheritance pattern. After identifying the cause of one branch as maternally inherited aminoglycoside-induced HL, targeted next generation sequencing (NGS) was applied to identify the genetic causes for the other two branches. One affected subject from each branch was subject to targeted NGS whose genomic DNA was enriched either by whole-exome capture (Agilent SureSelect All Exon 50 Mb) or by candidate genes capture (Agilent SureSelect custom kit). By NGS analysis, we identified that patients from Branch A were compound heterozygous for p.E1006K and p.D1663V in the CDH23 (DFNB12) gene; and patients from Branch B were homozygous for IVS7-2A>G in the SLC26A4 (DFNB4) gene. Both CDH23 mutations altered conserved calcium binding sites of the extracellular cadherin domains. The co-occurrence of three different genetic causes in this family was exceedingly rare but fully compatible with the mutation spectrum of HL. Our study has also raised several technical and analytical issues when applying the NGS technique to genetic testing. |
format | Online Article Text |
id | pubmed-4521291 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45212912015-08-07 Resolving the genetic heterogeneity of prelingual hearing loss within one family: Performance comparison and application of two targeted next generation sequencing approaches Lu, Yu Zhou, Xueya Jin, Zhanguo Cheng, Jing Shen, Weidong Ji, Fei Liu, Liyang Zhang, Xuegong Zhang, Michael Cao, Ye Han, Dongyi Choy, KwongWai Yuan, Huijun J Hum Genet Original Article Here, we report an unconventional Chinese pedigree consisting of three branches all segregating prelingual hearing loss (HL) with unclear inheritance pattern. After identifying the cause of one branch as maternally inherited aminoglycoside-induced HL, targeted next generation sequencing (NGS) was applied to identify the genetic causes for the other two branches. One affected subject from each branch was subject to targeted NGS whose genomic DNA was enriched either by whole-exome capture (Agilent SureSelect All Exon 50 Mb) or by candidate genes capture (Agilent SureSelect custom kit). By NGS analysis, we identified that patients from Branch A were compound heterozygous for p.E1006K and p.D1663V in the CDH23 (DFNB12) gene; and patients from Branch B were homozygous for IVS7-2A>G in the SLC26A4 (DFNB4) gene. Both CDH23 mutations altered conserved calcium binding sites of the extracellular cadherin domains. The co-occurrence of three different genetic causes in this family was exceedingly rare but fully compatible with the mutation spectrum of HL. Our study has also raised several technical and analytical issues when applying the NGS technique to genetic testing. Nature Publishing Group 2014-11 2014-09-18 /pmc/articles/PMC4521291/ /pubmed/25231367 http://dx.doi.org/10.1038/jhg.2014.78 Text en Copyright © 2014 The Japan Society of Human Genetics http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported 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/3.0/ |
spellingShingle | Original Article Lu, Yu Zhou, Xueya Jin, Zhanguo Cheng, Jing Shen, Weidong Ji, Fei Liu, Liyang Zhang, Xuegong Zhang, Michael Cao, Ye Han, Dongyi Choy, KwongWai Yuan, Huijun Resolving the genetic heterogeneity of prelingual hearing loss within one family: Performance comparison and application of two targeted next generation sequencing approaches |
title | Resolving the genetic heterogeneity of prelingual hearing loss within one family: Performance comparison and application of two targeted next generation sequencing approaches |
title_full | Resolving the genetic heterogeneity of prelingual hearing loss within one family: Performance comparison and application of two targeted next generation sequencing approaches |
title_fullStr | Resolving the genetic heterogeneity of prelingual hearing loss within one family: Performance comparison and application of two targeted next generation sequencing approaches |
title_full_unstemmed | Resolving the genetic heterogeneity of prelingual hearing loss within one family: Performance comparison and application of two targeted next generation sequencing approaches |
title_short | Resolving the genetic heterogeneity of prelingual hearing loss within one family: Performance comparison and application of two targeted next generation sequencing approaches |
title_sort | resolving the genetic heterogeneity of prelingual hearing loss within one family: performance comparison and application of two targeted next generation sequencing approaches |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521291/ https://www.ncbi.nlm.nih.gov/pubmed/25231367 http://dx.doi.org/10.1038/jhg.2014.78 |
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