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.