Whole Exome Sequencing Reveals a Mutation in CRYBB2 in a Large Mexican Family with Autosomal Dominant Pulverulent Cataract

Molecular Syndromology

Olga Messina-Baas¹  Jaime Toral-López¹  Luz M. González-Huerta¹  Sergio A. Cuevas-Covarrubias¹  Manuel L. Gonzalez-Garay¹ 

[1] aDepartments of Ophthalmology, Hospital General de México, Facultad de Medicina, UNAM, Mexico City, Mexico

关键词: Autosomal dominant pulverulent cataract;    Clinical heterogeneity;    CRYBB2;    CRYBB2P1;    Whole exome sequencing;   

DOI  :  10.1159/000445669

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

Congenital cataract, an important cause of reversible blindness, is due to several causes including Mendelian inheritance. Thirty percent of cataracts are hereditary with participation of the gamma crystallin genes. Clinical and genetic heterogeneity is observed in patients with gene mutations and congenital cataract; about 40 genetic loci have been associated with hereditary cataract. In this study, we identified the underlying genetic cause of an autosomal dominant pulverulent cataract (ADPC) in a large Mexican family. Twenty-one affected patients and 20 healthy members of a family with ADPC were included. Genomic DNA was analyzed by whole exome sequencing in the proband, a normal daughter, and in an affected son, whereas DNA Sanger sequencing was performed in all members of the family. After the bioinformatics analysis, all samples were genotyped using Sanger sequencing to eliminate variants that do not cosegregate with the cataract. We observed a perfect cosegregation of a nonsense mutation c.475C>T (p.Q155*) in exon 6 of the CRYBB2 gene with ADPC. We calculated a logarithm of the odds score of 5.5. This mutation was not detected in healthy members of the family and in 100 normal controls. This is the first Mexican family with ADPC associated with a p.Q155* mutation. Interestingly, this specific mutation in the CRYBB2 gene seems to be exclusively associated with pulverulent/cerulean cataract (with some clinical variability) independent of the population's genetic background.

【 授权许可】

Unknown