Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypes

Ciliopathies are a group of rare disorders characterized by a high genetic and phenotypic variability, which complicates their molecular diagnosis. Hence the need to use the latest powerful approaches to faster identify the genetic defect in these patients. We applied whole exome sequencing to six c...

Full description

Bibliographic Details
Authors: Castro Sánchez, Sheila, Álvarez Satta, María, Tohamy, Mohamed A., Beltran, Sergi, Derdak, Sophia, Valverde, Diana
Format: article
Status:Published version
Publication Date:2017
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/35045
Online Access:http://hdl.handle.net/10230/35045
http://dx.doi.org/10.1371/journal.pone.0183081
Access Level:Open access
Keyword:Genome analysis
Phenotype
Cilia
Gene sequencing
Ciliopathies
id ES_8f03b33732669f165c879441e7b69430
oai_identifier_str oai:recercat.cat:10230/35045
network_acronym_str ES
network_name_str España
repository_id_str
spelling Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypesCastro Sánchez, SheilaÁlvarez Satta, MaríaTohamy, Mohamed A.Beltran, SergiDerdak, SophiaValverde, DianaGenome analysisPhenotypeCiliaGene sequencingCiliopathiesCiliopathies are a group of rare disorders characterized by a high genetic and phenotypic variability, which complicates their molecular diagnosis. Hence the need to use the latest powerful approaches to faster identify the genetic defect in these patients. We applied whole exome sequencing to six consanguineous families clinically diagnosed with ciliopathy-like disease, and for which mutations in predominant Bardet-Biedl syndrome (BBS) genes had previously been excluded. Our strategy, based on first applying several filters to ciliary variants and using many of the bioinformatics tools available, allowed us to identify causal mutations in BBS2, ALMS1 and CRB1 genes in four families, thus confirming the molecular diagnosis of ciliopathy. In the remaining two families, after first rejecting the presence of pathogenic variants in common cilia-related genes, we adopted a new filtering strategy combined with prioritisation tools to rank the final candidate genes for each case. Thus, we propose CORO2B, LMO7 and ZNF17 as novel candidate ciliary genes, but further functional studies will be needed to confirm their role. Our data show the usefulness of this strategy to diagnose patients with unclear phenotypes, and therefore the success of applying such technologies to achieve a rapid and reliable molecular diagnosis, improving genetic counselling for these patients. In addition, the described pipeline also highlights the common pitfalls associated to the large volume of data we have to face and the difficulty of assigning a functional role to these changes, hence the importance of designing the most appropriate strategy according to each case.Public Library of Science (PLoS)201820182017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/35045http://dx.doi.org/10.1371/journal.pone.0183081reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésPLoS One. 2017 Aug 11;12(8):e0183081© 2017 Castro-Sánchez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/350452026-05-29T05:05:01Z
dc.title.none.fl_str_mv Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypes
title Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypes
spellingShingle Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypes
Castro Sánchez, Sheila
Genome analysis
Phenotype
Cilia
Gene sequencing
Ciliopathies
title_short Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypes
title_full Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypes
title_fullStr Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypes
title_full_unstemmed Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypes
title_sort Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypes
dc.creator.none.fl_str_mv Castro Sánchez, Sheila
Álvarez Satta, María
Tohamy, Mohamed A.
Beltran, Sergi
Derdak, Sophia
Valverde, Diana
author Castro Sánchez, Sheila
author_facet Castro Sánchez, Sheila
Álvarez Satta, María
Tohamy, Mohamed A.
Beltran, Sergi
Derdak, Sophia
Valverde, Diana
author_role author
author2 Álvarez Satta, María
Tohamy, Mohamed A.
Beltran, Sergi
Derdak, Sophia
Valverde, Diana
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Genome analysis
Phenotype
Cilia
Gene sequencing
Ciliopathies
topic Genome analysis
Phenotype
Cilia
Gene sequencing
Ciliopathies
description Ciliopathies are a group of rare disorders characterized by a high genetic and phenotypic variability, which complicates their molecular diagnosis. Hence the need to use the latest powerful approaches to faster identify the genetic defect in these patients. We applied whole exome sequencing to six consanguineous families clinically diagnosed with ciliopathy-like disease, and for which mutations in predominant Bardet-Biedl syndrome (BBS) genes had previously been excluded. Our strategy, based on first applying several filters to ciliary variants and using many of the bioinformatics tools available, allowed us to identify causal mutations in BBS2, ALMS1 and CRB1 genes in four families, thus confirming the molecular diagnosis of ciliopathy. In the remaining two families, after first rejecting the presence of pathogenic variants in common cilia-related genes, we adopted a new filtering strategy combined with prioritisation tools to rank the final candidate genes for each case. Thus, we propose CORO2B, LMO7 and ZNF17 as novel candidate ciliary genes, but further functional studies will be needed to confirm their role. Our data show the usefulness of this strategy to diagnose patients with unclear phenotypes, and therefore the success of applying such technologies to achieve a rapid and reliable molecular diagnosis, improving genetic counselling for these patients. In addition, the described pipeline also highlights the common pitfalls associated to the large volume of data we have to face and the difficulty of assigning a functional role to these changes, hence the importance of designing the most appropriate strategy according to each case.
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/35045
http://dx.doi.org/10.1371/journal.pone.0183081
url http://hdl.handle.net/10230/35045
http://dx.doi.org/10.1371/journal.pone.0183081
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv PLoS One. 2017 Aug 11;12(8):e0183081
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869413176370528256
score 15,812429

Similar Items