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dc.contributor.author
Tiwari, Amit
dc.contributor.author
Lemke, Johannes
dc.contributor.author
Altmueller, Janine
dc.contributor.author
Thiele, Holger
dc.contributor.author
Glaus, Esther
dc.contributor.author
Fleischhauer, Johannes
dc.contributor.author
Nürnberg, Peter
dc.contributor.author
Neidhardt, John
dc.contributor.author
Berger, Wolfgang
dc.date.accessioned
2018-08-30T09:18:25Z
dc.date.available
2017-06-12T09:34:21Z
dc.date.available
2018-08-30T09:18:25Z
dc.date.issued
2016-07-08
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0158692
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/118683
dc.identifier.doi
10.3929/ethz-b-000118683
dc.description.abstract
Inherited retinal dystrophies (IRDs) are Mendelian diseases with tremendous genetic and phenotypic heterogeneity. Identification of the underlying genetic basis of these dystrophies is therefore challenging. In this study we employed whole exome sequencing (WES) in 11 families with IRDs and identified disease-causing variants in 8 of them. Sequence analysis of about 250 IRD-associated genes revealed 3 previously reported disease-associated variants in RHO, BEST1 and RP1. We further identified 5 novel pathogenic variants in RPGRIP1 (p.Ser964Profs*37), PRPF8 (p.Tyr2334Leufs*51), CDHR1 (p.Pro133Arg and c.439-17G>A) and PRPF31 (p.Glu183_Met193dup). In addition to confirming the power of WES in genetic diagnosis of IRDs, we document challenges in data analysis and show cases where the underlying genetic causes of IRDs were missed by WES and required additional techniques. For example, the mutation c.439-17G>A in CDHR1 would be rated unlikely applying the standard WES analysis. Only transcript analysis in patient fibroblasts confirmed the pathogenic nature of this variant that affected splicing of CDHR1 by activating a cryptic splice-acceptor site. In another example, a 33-base pair duplication in PRPF31 missed by WES could be identified only via targeted analysis by Sanger sequencing. We discuss the advantages and challenges of using WES to identify mutations in heterogeneous diseases like IRDs.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Identification of Novel and Recurrent Disease-Causing Mutations in Retinal Dystrophies Using Whole Exome Sequencing (WES): Benefits and Limitations
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
PLoS ONE
ethz.journal.volume
11
en_US
ethz.journal.issue
7
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e0158692
en_US
ethz.size
17 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.identifier.nebis
006206116
ethz.publication.place
San Francisco, CA, USA
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-06-12T09:36:17Z
ethz.source
ECIT
ethz.identifier.importid
imp59365491cac1371296
ethz.ecitpid
pub:180648
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-14T12:07:07Z
ethz.rosetta.lastUpdated
2018-08-30T09:18:33Z
ethz.rosetta.versionExported
true
ethz.COinS
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