Combining targeted panel-based resequencing and copy-number variation analysis for the diagnosis of inherited syndromic retinopathies and associated ciliopathies

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dc.contributor.author Sánchez-Navarro, Iker
dc.contributor.author Da Silva, Luciana R.J.
dc.contributor.author Blanco-Kelly, Fiona
dc.contributor.author Zurita, Olga
dc.contributor.author Sánchez-Bolivar, Noelia
dc.contributor.author Villaverde, Cristina
dc.contributor.author López-Molina, María Isabel
dc.contributor.author García-Sandoval, Blanca
dc.contributor.author Tahsin-Swafiri, Saoud
dc.contributor.author Minguez, Pablo
dc.contributor.author Riveiro Álvarez, Rosa
dc.contributor.author Lorda, Isabel
dc.contributor.author Sánchez-Alcudia, Rocío
dc.contributor.author Pérez-Carro, Raquel
dc.contributor.author Valverde, Diana
dc.contributor.author Liu, Yichuan
dc.contributor.author Tian, Lifeng
dc.contributor.author Hakonarson, Hakon
dc.contributor.author Ávila-Fernández, Almudena
dc.contributor.author Corton, Marta
dc.contributor.author Ayuso, Carmen
dc.contributor.other UAM. Departamento de Cirugía es_ES
dc.contributor.other Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD) es_ES
dc.date.accessioned 2018-06-21T15:28:38Z
dc.date.available 2018-06-21T15:28:38Z
dc.date.issued 2018-12-01
dc.identifier.citation Scientific Reports 8 (2018): 5285 es_ES
dc.identifier.issn 2045-2322 es_ES
dc.identifier.uri http://hdl.handle.net/10486/683251
dc.description.abstract Inherited syndromic retinopathies are a highly heterogeneous group of diseases that involve retinal anomalies and systemic manifestations. They include retinal ciliopathies, other well-defined clinical syndromes presenting with retinal alterations and cases of non-specific multisystemic diseases. The heterogeneity of these conditions makes molecular and clinical characterization of patients challenging in daily clinical practice. We explored the capacity of targeted resequencing and copy-number variation analysis to improve diagnosis of a heterogeneous cohort of 47 patients mainly comprising atypical cases that did not clearly fit a specific clinical diagnosis. Thirty-three likely pathogenic variants were identified in 18 genes (ABCC6, ALMS1, BBS1, BBS2, BBS12, CEP41, CEP290, IFT172, IFT27, MKKS, MYO7A, OTX2, PDZD7, PEX1, RPGRIP1, USH2A, VPS13B, and WDPCP). Molecular findings and additional clinical reassessments made it possible to accurately characterize 14 probands (30% of the total). Notably, clinical refinement of complex phenotypes was achieved in 4 cases, including 2 de novo OTX2-related syndromes, a novel phenotypic association for the ciliary CEP41 gene, and the co-existence of biallelic USH2A variants and a Koolen-de-Vries syndrome-related 17q21.31 microdeletion. We demonstrate that combining next-generation sequencing and CNV analysis is a comprehensive and useful approach to unravel the extensive phenotypic and genotypic complexity of inherited syndromic retinopathies en_US
dc.description.sponsorship This study was funded by several grants from the Instituto de Salud Carlos III (ISCIII) from the Spanish Ministry of Health, including CIBERER (06/07/0036), FIS - FEDER (European Regional Development Fund) (PI016/00425), IIS-FJD Biobank PT13/0010/0012. In addition, sponsored chair HU-FJD-UAM “Cátedra de Patrocinio Medicina Genómica”, the Spanish National Organization of the Blind (ONCE) and the Spanish Fighting Blindness Foundation (FUNDALUCE) also supported our work. ISN and RSA are sponsored by Sara Borrell Postdoctoral Program (CD13-00085 and CD12-00676) from ISCIII/FEDER. MC is supported by the Miguel Servet Program (CP12/03256) from ISCIII/FEDER. RPC is supported by Fundación Conchita Rábago and LRJS is supported by CAPES Foundation, Ministry of Education of Brazil en_US
dc.format.extent 11 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher Nature Publishing Group en_US
dc.relation.ispartof Scientific Reports en_US
dc.rights © 2018 The Author(s) es_ES
dc.subject.other Retinopathies en_US
dc.subject.other Retinal ciliopathies en_US
dc.subject.other 18 genes en_US
dc.subject.other Ciliary CEP41 gene en_US
dc.subject.other Phenotypic and genotypic en_US
dc.title Combining targeted panel-based resequencing and copy-number variation analysis for the diagnosis of inherited syndromic retinopathies and associated ciliopathies en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion https://doi.org/10.1038/s41598-018-23520-1 es_ES
dc.identifier.doi 10.1038/s41598-018-23520-1 es_ES
dc.identifier.publicationfirstpage 5285-1 es_ES
dc.identifier.publicationissue 8 es_ES
dc.identifier.publicationlastpage 5285-11 es_ES
dc.relation.projectID Gobierno de España. PI016/00425 es_ES
dc.relation.projectID Gobierno de España. PT13/0010/0012 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en


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