Mutation analysis of congenital cataract in a Basotho family identified a new missense allele in CRYBB2

[摘要] Purpose: To identify the causativegenetic mutation among the known cataract candidate genes underlyingthe observed phenotype in a Basotho family, with congenital nuclearcataracts. Methods: Because of the small familysize, we used the functional candidate gene analysis approach. Wescreened a Basotho family, clinically documented to have congenitalnuclear 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 chainreaction analyses and sequencing. Results: Mutation screening identifiedonly one significant alteration in exon 6 (607G>A) of CRYBB2,with a substitution of Valine to Methionine at position 187. Thismutation segregated in all five affected family members but it was notobserved in any of the unaffected persons of the family. The putativemutation led also to the appearance of a new NIaIII restriction site inthe samples of the affected family members that was not present in 100randomly selected DNA samples from ophthalmologically normalindividuals and in 40 unrelated senile cataract patients of the sameethnic background as the family members. Conclusions: This study identified amissense mutation in CRYBB2 in a family of Basotho withautosomal dominant congenital cataract (ADCC). In summary, we believethis new missense allele is the probable causative molecular lesion forthe observed phenotype in this family.

[学科分类] 生物化学/生物物理