High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population

Orphanet Journal of Rare Diseases

Carmen Ayuso²  Montserrat Baiget²  Blanca García-Sandoval²  Sara Bernal²  Rosa Riveiro-Alvarez²  Fiona Blanco-Kelly²  Diego Cantalapiedra²  Ignacio Tapias¹  Elena Vallespín²  Almudena Avila-Fernandez²  Sorina D Tatu²  Marta Corton² 

[1] Department of Ophthalmology, Fundación Jiménez Díaz, Madrid, Spain;Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Valencia, Spain

关键词: High resolution melting;    Homozygosity mapping;    CRB1;    Early-onset retinitis pigmentosa;    Leber congenital amaurosis;   

Others  :  864128
DOI  :  10.1186/1750-1172-8-20

 received in 2012-05-06, accepted in 2013-01-26,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Corton et al.; licensee BioMed Central Ltd.

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