Two Chinese families with pulverulent congenital cataracts and deltaG91 CRYBA1 mutations.

PURPOSE: To characterize the disease-causing mutations and related phenotypes in two Chinese families with autosomal dominant congenital cataract.

METHODS

Family members were clinically characterized by a complete eye examination. Genome-wide linkage screening was performed in Family 1 using a 10K single nucleotide polymorphism approach followed by genotyping of microsatellite markers from the regions with highest support for linkage. The candidate gene, betaA1-crystallin (CRYBA1), was sequenced in both families.

RESULTS

Lens examinations in three affected phakic members showed bilateral pulverulent nuclear cataracts in two subjects of Family 1 while another subject of Family 2 displayed bilateral pulverulent lamellar cataract. Linkage analysis in 14 individuals (eight affected, three unaffected and three of their spouses) of Family 1 gave a maximum logarithm of odds score of 2.41 for D17S1294 in chromosomal region 17q11.12 that includes the CRYBA1 gene. In both families in-frame deletions of three bp were detected in exon 4 of CRYBA1 leading to loss of a guanine residue (deltaG91). The mutations cosegregated completely with the cataract phenotype in both families but were associated with distinct haplotypes suggesting that they had occurred independently.

CONCLUSIONS

The previously described CRYBA1 mutation deltaG91 was demonstrated in two Chinese families with distinct phenotypes of congenital cataract, suggesting a lack of genotype-phenotype correlation. The findings also raise the possibility that the delta91 mutation arise in a relatively mutation-prone sequence of the CRYBA1 gene.