Purpose: To identify ultrastructure changes and genetic defects associated with a special fasciculiform autosomal dominant congenital cataract (ADCC) affecting a large Chinese family.
Methods: Members of the Chinese family affected by this special fasciculiform ADCC were studied. Clinical examinations, light and transmission electron microscopy of the removed lens tissue, linkage analyses using polymorphisms of microsatellite markers, and mutational analyses of candidate genes by direct sequencing were performed.
Results: The thirteen affected individuals in the family showed no variability between one another. The lens fiber cells showed focal degeneration, dense globular intracellular deposits, and an enlarged intercellular space. This ADCC was associated with a locus on chromosome 2q33-35 (maximum lod score [Zmax]=3.34; theta=0.05). Mutational analyses of the candidate genes (gamma-crystallin; CRYG), identified a C->A heterozygous transversion at nucleotide position 70 in the gammaD-crystallin gene (CRYGD) exon2, which co-segregated with the presence of ADCCs and was not observed in 100 unrelated controls.
Conclusions: This study identified ultrastructure changes and genetic defects associated with a special fasciculiform ADCC affecting a large Chinese family. It appeared to be caused by a missense mutation in the CRYGD gene, further supporting the notion that alterations to CRYG play an important factor in human cataract formation.