Purpose: To identify the causative genetic mutation among the known cataract candidate genes underlying the observed phenotype in a Basotho family, with congenital nuclear cataracts.
Methods: Because of the small family size, we used the functional candidate gene analysis approach. We screened a Basotho family, clinically documented to have congenital nuclear cataracts, for mutation in the candidate genes CRYG (C & D; Crystallin, gamma C and Crystallin, gamma D), GJA8 (Gap junction protein, alpha 8), CRY (AA & AB; Crystallin, alpha A and Crystallin, alpha B), CRYBA (Crystallin, beta A) and CRY (BB1 & BB2; Crystallin, beta B1 and Crystallin, beta B2) through polymerase chain reaction analyses and sequencing.
Results: Mutation screening identified only one significant alteration in exon 6 (607G>A) of CRYBB2, with a substitution of Valine to Methionine at position 187. This mutation segregated in all five affected family members but it was not observed in any of the unaffected persons of the family. The putative mutation led also to the appearance of a new NIaIII restriction site in the samples of the affected family members that was not present in 100 randomly selected DNA samples from ophthalmologically normal individuals and in 40 unrelated senile cataract patients of the same ethnic background as the family members.
Conclusions: This study identified a missense mutation in CRYBB2 in a family of Basotho with autosomal dominant congenital cataract (ADCC). In summary, we believe this new missense allele is the probable causative molecular lesion for the observed phenotype in this family.