High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population
Corton, Marta (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
Tatu, Sorina D. (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
Avila-Fernandez, Almudena (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
Vallespín, Elena (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
Tapias, Ignacio (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
Cantalapiedra, Diego (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
Blanco-Kelly, Fiona (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
Riveiro-Alvarez, Rosa (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
Bernal, Sara (Institut d'Investigació Biomèdica Sant Pau)
García-Sandoval, Blanca (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
Baiget Bastús, Montserrat (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Ayuso, Carmen (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Universitat Autònoma de Barcelona

Data:	2013
Resum:	Background: CRB1 mutations are reported as cause of severe congenital and early-onset retinal dystrophies (EORD) with different phenotypic manifestations, including Leber congenital amaurosis (LCA), retinitis pigmentosa (RP) and cone-rod dystrophies. Comprehensive mutational scanning of the whole gene has been only performed in few cohorts, mainly in LCA patients. Here, we aimed investigating the real prevalence of CRB1 mutations in the Spanish population by extensive screening of CRB1 mutations in a large cohort of LCA and EORP cases. Methods. This report integrates data from previous studies on CRB1 defects in our Spanish cohort of LCA and early-onset RP (EORP) with new findings from a comprehensive mutational screening of the whole gene. The molecular tools used include mutation genotyping arrays, whole-genome homozygosity mapping, an optimized high-resolution melting (HRM) analysis and Sanger sequencing. Results: A large clinically well-characterized cohort of 404 Spanish cases was studied, 114 of which suffered from LCA and 290 from EORP. This study reveals that 11% of Spanish patients carried mutations in CRB1, ranging from 9% of EORP to 14% of LCA cases. More than three quarters of the mutations identified herein have been first described in this Spanish cohort, 13 of them are unreported new variants and 13 had been previously reported in our previous studies. Conclusions: This work provides a wide spectrum of CRB1 mutations in the Spanish EORD patients and evidences the major role of CRB1 as causal gene in the Spanish EORP patients. It is noteworthy that a high rate of private mutations only described in our cohort has been found so far. To our knowledge, this study represents the most complete mutational screening of CRB1 in a Spanish LCA and EORP cohort, allowing us to establish gene-specific frequencies and to provide a wide spectrum of CRB1 mutations in the Spanish population. © 2013 Corton et al. ; licensee BioMed Central Ltd.
Ajuts:	Ministerio de Ciencia e Innovación PS09/00459 Ministerio de Ciencia e Innovación RD09-0076-00101
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Orphanet journal of rare diseases, Vol. 8 Núm. 1 (2013) , p. 20, ISSN 1750-1172

DOI: 10.1186/1750-1172-8-20
PMID: 23379534

12 p, 368.5 KB

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