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DNA diagnostics of hereditary hearing loss: a targeted resequencing approach combined with a mutation classification system

Manou Sommen, Isabelle Schrauwen, Geert Vandeweyer, Nele Boeckx, Jason J Corneveaux, Jenneke van den Ende, An Boudewyns, Els De Leenheer UGent, Sandra Janssens UGent, Kathleen Claes UGent, et al. (2016) HUMAN MUTATION. 37(8). p.812-819
abstract
Although there are nearly 100 different causative genes identified for nonsyndromic hearing loss (NSHL), Sanger sequencing-based DNA diagnostics usually only analyses three, namely, GJB2, SLC26A4, and OTOF. As this is seen as inadequate, there is a need for high-throughput diagnostic methods to detect disease-causing variations, including single-nucleotide variations (SNVs), insertions/deletions (Indels), and copy-number variations (CNVs). In this study, a targeted resequencing panel for hearing loss was developed including 79 genes for NSHL and selected forms of syndromic hearing loss. One-hundred thirty one presumed autosomal-recessive NSHL (arNSHL) patients of Western-European ethnicity were analyzed for SNVs, Indels, and CNVs. In addition, we established a straightforward variant classification system to deal with the large number of variants encountered. We estimate that combining prescreening of GJB2 with our panel leads to a diagnosis in 25%-30% of patients. Our data show that after GJB2, the most commonly mutated genes in a Western-European population are TMC1, MYO15A, and MYO7A (3.1%). CNV analysis resulted in the identification of causative variants in two patients in OTOA and STRC. One of the major challenges for diagnostic gene panels is assigning pathogenicity for variants. A collaborative database collecting all identified variants from multiple centers could be a valuable resource for hearing loss diagnostics.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
mutation classification system, targeted resequencing, hereditary hearing loss, INTEGRATIVE GENOMICS VIEWER, DEAF MUTISM, PROTEIN FUNCTION, PENDRED-SYNDROME, SEQUENCING DATA, NGS DATA, VARIANTS, GENES, SPECTRUM, POPULATION
journal title
HUMAN MUTATION
Hum. Mutat.
volume
37
issue
8
pages
812 - 819
Web of Science type
Article
Web of Science id
000379932300012
JCR category
GENETICS & HEREDITY
JCR impact factor
4.601 (2016)
JCR rank
29/166 (2016)
JCR quartile
1 (2016)
ISSN
1059-7794
DOI
10.1002/humu.22999
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
8050407
handle
http://hdl.handle.net/1854/LU-8050407
date created
2016-08-18 08:11:51
date last changed
2017-06-12 10:06:50
@article{8050407,
  abstract     = {Although there are nearly 100 different causative genes identified for nonsyndromic hearing loss (NSHL), Sanger sequencing-based DNA diagnostics usually only analyses three, namely, GJB2, SLC26A4, and OTOF. As this is seen as inadequate, there is a need for high-throughput diagnostic methods to detect disease-causing variations, including single-nucleotide variations (SNVs), insertions/deletions (Indels), and copy-number variations (CNVs). In this study, a targeted resequencing panel for hearing loss was developed including 79 genes for NSHL and selected forms of syndromic hearing loss. One-hundred thirty one presumed autosomal-recessive NSHL (arNSHL) patients of Western-European ethnicity were analyzed for SNVs, Indels, and CNVs. In addition, we established a straightforward variant classification system to deal with the large number of variants encountered. We estimate that combining prescreening of GJB2 with our panel leads to a diagnosis in 25\%-30\% of patients. Our data show that after GJB2, the most commonly mutated genes in a Western-European population are TMC1, MYO15A, and MYO7A (3.1\%). CNV analysis resulted in the identification of causative variants in two patients in OTOA and STRC. One of the major challenges for diagnostic gene panels is assigning pathogenicity for variants. A collaborative database collecting all identified variants from multiple centers could be a valuable resource for hearing loss diagnostics.},
  author       = {Sommen, Manou and Schrauwen, Isabelle and Vandeweyer, Geert and Boeckx, Nele and Corneveaux, Jason J and van den Ende, Jenneke and Boudewyns, An and De Leenheer, Els and Janssens, Sandra and Claes, Kathleen and Verstreken, Margriet and Strenzke, Nicola and Pred{\"o}hl, Friderike and Wuyts, Wim and Mortier, Geert and Bitner-Glindzicz, Maria and Moser, Tobias and Coucke, Paul and Huentelman, Matthew J and Van Camp, Guy},
  issn         = {1059-7794},
  journal      = {HUMAN MUTATION},
  keyword      = {mutation classification system,targeted resequencing,hereditary hearing loss,INTEGRATIVE GENOMICS VIEWER,DEAF MUTISM,PROTEIN FUNCTION,PENDRED-SYNDROME,SEQUENCING DATA,NGS DATA,VARIANTS,GENES,SPECTRUM,POPULATION},
  language     = {eng},
  number       = {8},
  pages        = {812--819},
  title        = {DNA diagnostics of hereditary hearing loss: a targeted resequencing approach combined with a mutation classification system},
  url          = {http://dx.doi.org/10.1002/humu.22999},
  volume       = {37},
  year         = {2016},
}

Chicago
Sommen, Manou, Isabelle Schrauwen, Geert Vandeweyer, Nele Boeckx, Jason J Corneveaux, Jenneke van den Ende, An Boudewyns, et al. 2016. “DNA Diagnostics of Hereditary Hearing Loss: a Targeted Resequencing Approach Combined with a Mutation Classification System.” Human Mutation 37 (8): 812–819.
APA
Sommen, M., Schrauwen, I., Vandeweyer, G., Boeckx, N., Corneveaux, J. J., van den Ende, J., Boudewyns, A., et al. (2016). DNA diagnostics of hereditary hearing loss: a targeted resequencing approach combined with a mutation classification system. HUMAN MUTATION, 37(8), 812–819.
Vancouver
1.
Sommen M, Schrauwen I, Vandeweyer G, Boeckx N, Corneveaux JJ, van den Ende J, et al. DNA diagnostics of hereditary hearing loss: a targeted resequencing approach combined with a mutation classification system. HUMAN MUTATION. 2016;37(8):812–9.
MLA
Sommen, Manou, Isabelle Schrauwen, Geert Vandeweyer, et al. “DNA Diagnostics of Hereditary Hearing Loss: a Targeted Resequencing Approach Combined with a Mutation Classification System.” HUMAN MUTATION 37.8 (2016): 812–819. Print.