Purpose: We sought to identify the genetic defect in a four-generation Chinese family with autosomal dominant congenital nuclear cataracts, examine the clinical features in detail and demonstrate the functional analysis of a candidate gene in the family.
Methods: Family history data were recorded. Clinical and ophthalmological examinations were performed on affected and unaffected family members. All the members were genotyped with microsatellite markers at loci considered to be associated with cataracts. Two-point LOD scores were calculated using the LINKAGE program package after genotyping. A mutation was detected by dilff521229rect sequencing and verified by denaturing high-performance liquid chromatography (DHPLC). Wild-type and mutant proteins were analyzed with online softwares.
Results: All affected members of this family had nuclear cataracts. Genetic analysis revealed a heterozygous previously described Arg116Cys mutation in the CRYAA gene in all of the affected members of the family but not in unaffected or 100 normal, unrelated individuals. Data generated with online software revealed that the different amino acid side chain, impact the aa116 interaction with other amino acids, thereby affecting the proteins secondary structure.
Conclusions: This study identified a mutation in the CRYAA gene causing autosomal dominant nuclear cataracts and some patients show nystagmus or small blepharophimosis clinical features. These results provide evidence that CRYAA is a pathogenic gene for congenital cataracts, congenital cataracts are a clinically and genetically heterogeneous lens condition; at the same time, demonstrates a possible mechanism of action for the mutant gene.