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High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population
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 ge...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637806/ https://www.ncbi.nlm.nih.gov/pubmed/23379534 http://dx.doi.org/10.1186/1750-1172-8-20 |
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author | Corton, Marta Tatu, Sorina D Avila-Fernandez, Almudena Vallespín, Elena Tapias, Ignacio Cantalapiedra, Diego Blanco-Kelly, Fiona Riveiro-Alvarez, Rosa Bernal, Sara García-Sandoval, Blanca Baiget, Montserrat Ayuso, Carmen |
author_facet | Corton, Marta Tatu, Sorina D Avila-Fernandez, Almudena Vallespín, Elena Tapias, Ignacio Cantalapiedra, Diego Blanco-Kelly, Fiona Riveiro-Alvarez, Rosa Bernal, Sara García-Sandoval, Blanca Baiget, Montserrat Ayuso, Carmen |
author_sort | Corton, Marta |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3637806 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36378062013-04-28 High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population Corton, Marta Tatu, Sorina D Avila-Fernandez, Almudena Vallespín, Elena Tapias, Ignacio Cantalapiedra, Diego Blanco-Kelly, Fiona Riveiro-Alvarez, Rosa Bernal, Sara García-Sandoval, Blanca Baiget, Montserrat Ayuso, Carmen Orphanet J Rare Dis Research 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. BioMed Central 2013-02-05 /pmc/articles/PMC3637806/ /pubmed/23379534 http://dx.doi.org/10.1186/1750-1172-8-20 Text en Copyright © 2013 Corton et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Corton, Marta Tatu, Sorina D Avila-Fernandez, Almudena Vallespín, Elena Tapias, Ignacio Cantalapiedra, Diego Blanco-Kelly, Fiona Riveiro-Alvarez, Rosa Bernal, Sara García-Sandoval, Blanca Baiget, Montserrat Ayuso, Carmen High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population |
title | High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population |
title_full | High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population |
title_fullStr | High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population |
title_full_unstemmed | High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population |
title_short | High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population |
title_sort | high frequency of crb1 mutations as cause of early-onset retinal dystrophies in the spanish population |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637806/ https://www.ncbi.nlm.nih.gov/pubmed/23379534 http://dx.doi.org/10.1186/1750-1172-8-20 |
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