Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies

Inherited monogenic diseases of the retina and vitreous affect approximately 1 in 2000 individuals. They are characterized by tremendous genetic heterogeneity and clinical variability involving mutations in approximately 250 genes and more than 20 different clinical phenotypes. Clinical manifestatio...

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Main Authors:	Tiwari, Amit, Bahr, Angela, Bähr, Luzy, Fleischhauer, Johannes, Zinkernagel, Martin S., Winkler, Niklas, Barthelmes, Daniel, Berger, Lieselotte, Gerth-Kahlert, Christina, Neidhardt, John, Berger, Wolfgang
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926080/

id	pubmed-4926080
recordtype	oai_dc
spelling	pubmed-49260802016-06-29 Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies Tiwari, Amit Bahr, Angela Bähr, Luzy Fleischhauer, Johannes Zinkernagel, Martin S. Winkler, Niklas Barthelmes, Daniel Berger, Lieselotte Gerth-Kahlert, Christina Neidhardt, John Berger, Wolfgang Article Inherited monogenic diseases of the retina and vitreous affect approximately 1 in 2000 individuals. They are characterized by tremendous genetic heterogeneity and clinical variability involving mutations in approximately 250 genes and more than 20 different clinical phenotypes. Clinical manifestations of retinal dystrophies (RDs) range from mild retinal dysfunctions to severe congenital forms of blindness. A detailed clinical diagnosis and the identification of causative mutations are crucial for genetic counseling of affected patients and their families, for understanding genotype-phenotype correlations and developing therapeutic approaches. Using whole exome sequencing (WES) we have established a reliable and efficient high-throughput analysis pipeline to identify disease-causing mutations. Our data indicate that this approach enables us to genetically diagnose approximately 64% of the patients (n = 58) with variant(s) in known disease-associated genes. We report 20 novel and 26 recurrent variants in genes associated with RDs. We also identified a novel phenotype for mutations in C2orf71 and provide functional evidence for exon skipping due to a splice-site variant identified in FLVCR1. In conclusion, WES can rapidly identify variants in various families affected with different forms of RDs. Our study also expands the clinical and allelic spectrum of genes associated with RDs in the Swiss population. Nature Publishing Group 2016-06-29 /pmc/articles/PMC4926080/ /pubmed/27353947 http://dx.doi.org/10.1038/srep28755 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International 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/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Tiwari, Amit Bahr, Angela Bähr, Luzy Fleischhauer, Johannes Zinkernagel, Martin S. Winkler, Niklas Barthelmes, Daniel Berger, Lieselotte Gerth-Kahlert, Christina Neidhardt, John Berger, Wolfgang
spellingShingle	Tiwari, Amit Bahr, Angela Bähr, Luzy Fleischhauer, Johannes Zinkernagel, Martin S. Winkler, Niklas Barthelmes, Daniel Berger, Lieselotte Gerth-Kahlert, Christina Neidhardt, John Berger, Wolfgang Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies
author_facet	Tiwari, Amit Bahr, Angela Bähr, Luzy Fleischhauer, Johannes Zinkernagel, Martin S. Winkler, Niklas Barthelmes, Daniel Berger, Lieselotte Gerth-Kahlert, Christina Neidhardt, John Berger, Wolfgang
author_sort	Tiwari, Amit
title	Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies
title_short	Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies
title_full	Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies
title_fullStr	Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies
title_full_unstemmed	Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies
title_sort	next generation sequencing based identification of disease-associated mutations in swiss patients with retinal dystrophies
description	Inherited monogenic diseases of the retina and vitreous affect approximately 1 in 2000 individuals. They are characterized by tremendous genetic heterogeneity and clinical variability involving mutations in approximately 250 genes and more than 20 different clinical phenotypes. Clinical manifestations of retinal dystrophies (RDs) range from mild retinal dysfunctions to severe congenital forms of blindness. A detailed clinical diagnosis and the identification of causative mutations are crucial for genetic counseling of affected patients and their families, for understanding genotype-phenotype correlations and developing therapeutic approaches. Using whole exome sequencing (WES) we have established a reliable and efficient high-throughput analysis pipeline to identify disease-causing mutations. Our data indicate that this approach enables us to genetically diagnose approximately 64% of the patients (n = 58) with variant(s) in known disease-associated genes. We report 20 novel and 26 recurrent variants in genes associated with RDs. We also identified a novel phenotype for mutations in C2orf71 and provide functional evidence for exon skipping due to a splice-site variant identified in FLVCR1. In conclusion, WES can rapidly identify variants in various families affected with different forms of RDs. Our study also expands the clinical and allelic spectrum of genes associated with RDs in the Swiss population.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926080/
_version_	1613601266995298304

Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies

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