Special fasciculiform cataract caused by a mutation in the γD-crystallin gene

[摘要] Purpose: To identify ultrastructure changes and genetic defectsassociated with a special fasciculiform autosomal dominant congenitalcataract (ADCC) affecting a large Chinese family.Methods: Members of the Chinese family affected by this specialfasciculiform ADCC were studied. Clinical examinations, light andtransmission electron microscopy of the removed lens tissue, linkageanalyses using polymorphisms of microsatellite markers, and mutationalanalyses of candidate genes by direct sequencing were performed.Results: The thirteen affected individuals in the family showed novariability between one another. The lens fiber cells showed focaldegeneration, dense globular intracellular deposits, and an enlargedintercellular space. This ADCC was associated with a locus on chromosome2q33-35 (maximum lod score [Zmax]=3.34; θ=0.05). Mutationalanalyses of the candidate genes (γ-crystallin; CRYG),identified a C->A heterozygous transversion at nucleotide position 70in the γD-crystallin gene (CRYGD) exon2, which co-segregatedwith the presence of ADCCs and was not observed in 100 unrelatedcontrols.Conclusions: This study identified ultrastructure changes andgenetic defects associated with a special fasciculiform ADCC affecting alarge Chinese family. It appeared to be caused by a missense mutation inthe CRYGD gene, further supporting the notion that alterations toCRYG play an important factor in human cataract formation.

[学科分类] 生物化学/生物物理