Cargando…
Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations
PURPOSE: Targeted next-generation sequencing provides a remarkable opportunity to identify variants in known disease genes, particularly in extremely heterogeneous disorders such as nonsyndromic hearing loss. The present study attempts to shed light on the complexity of hearing impairment. METHODS:...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262760/ https://www.ncbi.nlm.nih.gov/pubmed/24875298 http://dx.doi.org/10.1038/gim.2014.65 |
_version_ | 1782348461092372480 |
---|---|
author | Vona, Barbara Müller, Tobias Nanda, Indrajit Neuner, Cordula Hofrichter, Michaela A. H. Schröder, Jörg Bartsch, Oliver Läßig, Anne Keilmann, Annerose Schraven, Sebastian Kraus, Fabian Shehata-Dieler, Wafaa Haaf, Thomas |
author_facet | Vona, Barbara Müller, Tobias Nanda, Indrajit Neuner, Cordula Hofrichter, Michaela A. H. Schröder, Jörg Bartsch, Oliver Läßig, Anne Keilmann, Annerose Schraven, Sebastian Kraus, Fabian Shehata-Dieler, Wafaa Haaf, Thomas |
author_sort | Vona, Barbara |
collection | PubMed |
description | PURPOSE: Targeted next-generation sequencing provides a remarkable opportunity to identify variants in known disease genes, particularly in extremely heterogeneous disorders such as nonsyndromic hearing loss. The present study attempts to shed light on the complexity of hearing impairment. METHODS: Using one of two next-generation sequencing panels containing either 80 or 129 deafness genes, we screened 30 individuals with nonsyndromic hearing loss (from 23 unrelated families) and analyzed 9 normal-hearing controls. RESULTS: Overall, we found an average of 3.7 variants (in 80 genes) with deleterious prediction outcome, including a number of novel variants, in individuals with nonsyndromic hearing loss and 1.4 in controls. By next-generation sequencing alone, 12 of 23 (52%) probands were diagnosed with monogenic forms of nonsyndromic hearing loss; one individual displayed a DNA sequence mutation together with a microdeletion. Two (9%) probands have Usher syndrome. In the undiagnosed individuals (10/23; 43%) we detected a significant enrichment of potentially pathogenic variants as compared to controls. CONCLUSION: Next-generation sequencing combined with microarrays provides the diagnosis for approximately half of the GJB2 mutation–negative individuals. Usher syndrome was found to be more frequent in the study cohort than anticipated. The conditions in a proportion of individuals with nonsyndromic hearing loss, particularly in the undiagnosed group, may have been caused or modified by an accumulation of unfavorable variants across multiple genes. |
format | Online Article Text |
id | pubmed-4262760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-42627602014-12-16 Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations Vona, Barbara Müller, Tobias Nanda, Indrajit Neuner, Cordula Hofrichter, Michaela A. H. Schröder, Jörg Bartsch, Oliver Läßig, Anne Keilmann, Annerose Schraven, Sebastian Kraus, Fabian Shehata-Dieler, Wafaa Haaf, Thomas Genet Med Original Research Article PURPOSE: Targeted next-generation sequencing provides a remarkable opportunity to identify variants in known disease genes, particularly in extremely heterogeneous disorders such as nonsyndromic hearing loss. The present study attempts to shed light on the complexity of hearing impairment. METHODS: Using one of two next-generation sequencing panels containing either 80 or 129 deafness genes, we screened 30 individuals with nonsyndromic hearing loss (from 23 unrelated families) and analyzed 9 normal-hearing controls. RESULTS: Overall, we found an average of 3.7 variants (in 80 genes) with deleterious prediction outcome, including a number of novel variants, in individuals with nonsyndromic hearing loss and 1.4 in controls. By next-generation sequencing alone, 12 of 23 (52%) probands were diagnosed with monogenic forms of nonsyndromic hearing loss; one individual displayed a DNA sequence mutation together with a microdeletion. Two (9%) probands have Usher syndrome. In the undiagnosed individuals (10/23; 43%) we detected a significant enrichment of potentially pathogenic variants as compared to controls. CONCLUSION: Next-generation sequencing combined with microarrays provides the diagnosis for approximately half of the GJB2 mutation–negative individuals. Usher syndrome was found to be more frequent in the study cohort than anticipated. The conditions in a proportion of individuals with nonsyndromic hearing loss, particularly in the undiagnosed group, may have been caused or modified by an accumulation of unfavorable variants across multiple genes. Nature Publishing Group 2014-12 2014-05-29 /pmc/articles/PMC4262760/ /pubmed/24875298 http://dx.doi.org/10.1038/gim.2014.65 Text en Copyright © 2014 American College of Medical Genetics and Genomics http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 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/3.0/ |
spellingShingle | Original Research Article Vona, Barbara Müller, Tobias Nanda, Indrajit Neuner, Cordula Hofrichter, Michaela A. H. Schröder, Jörg Bartsch, Oliver Läßig, Anne Keilmann, Annerose Schraven, Sebastian Kraus, Fabian Shehata-Dieler, Wafaa Haaf, Thomas Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations |
title | Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations |
title_full | Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations |
title_fullStr | Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations |
title_full_unstemmed | Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations |
title_short | Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations |
title_sort | targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262760/ https://www.ncbi.nlm.nih.gov/pubmed/24875298 http://dx.doi.org/10.1038/gim.2014.65 |
work_keys_str_mv | AT vonabarbara targetednextgenerationsequencingofdeafnessgenesinhearingimpairedindividualsuncoversinformativemutations AT mullertobias targetednextgenerationsequencingofdeafnessgenesinhearingimpairedindividualsuncoversinformativemutations AT nandaindrajit targetednextgenerationsequencingofdeafnessgenesinhearingimpairedindividualsuncoversinformativemutations AT neunercordula targetednextgenerationsequencingofdeafnessgenesinhearingimpairedindividualsuncoversinformativemutations AT hofrichtermichaelaah targetednextgenerationsequencingofdeafnessgenesinhearingimpairedindividualsuncoversinformativemutations AT schroderjorg targetednextgenerationsequencingofdeafnessgenesinhearingimpairedindividualsuncoversinformativemutations AT bartscholiver targetednextgenerationsequencingofdeafnessgenesinhearingimpairedindividualsuncoversinformativemutations AT laßiganne targetednextgenerationsequencingofdeafnessgenesinhearingimpairedindividualsuncoversinformativemutations AT keilmannannerose targetednextgenerationsequencingofdeafnessgenesinhearingimpairedindividualsuncoversinformativemutations AT schravensebastian targetednextgenerationsequencingofdeafnessgenesinhearingimpairedindividualsuncoversinformativemutations AT krausfabian targetednextgenerationsequencingofdeafnessgenesinhearingimpairedindividualsuncoversinformativemutations AT shehatadielerwafaa targetednextgenerationsequencingofdeafnessgenesinhearingimpairedindividualsuncoversinformativemutations AT haafthomas targetednextgenerationsequencingofdeafnessgenesinhearingimpairedindividualsuncoversinformativemutations |