Genetically distinct autosomal dominant posterior polar cataract in a four-generation Japanese family.

Purpose: To describe the clinical findings of a form of posterior polar cataract in a large Japanese family and to determine whether the posterior polar cataract is causally related to other autosomal dominant cataracts with known genes, chromosomal locations, or both.

Methods: Systemic and ocular histories were obtained and comprehensive ophthalmic examinations were performed in 15 of 37 members of the Japanese family. The posterior polar cataract was transmitted in an autosomal dominant manner through four generations. Although there is some variation in the degree of opacification, the posterior polar cataract in this family is characterized by progressive disk-shaped posterior subcapsular opacities. Genetic linkage analysis was performed with 41 polymorphic microsatellite markers located in chromosomal regions known for linkage to cataracts. Genomic DNA extracted from the 15 individuals was amplified by polymerase chain reaction, the genotype at the marker loci was determined in each family member, and the lod score was calculated at each locus.

Results: Significant linkage of the posterior polar cataract was ruled out from the following 10 loci or chromosomal regions: 16q22 and 1p36, to which two forms of autosomal dominant posterior polar cataract have been assigned: 1q21-q25, 2q33-q35, 13cen, 17p13, 17q11-q12, 17q24, 21q22, and 22q, which are the regions responsible for other autosomal dominant congenital cataracts.

Conclusions: This study confirms the genetic heterogeneity of autosomal dominant posterior polar cataracts and demonstrates that the posterior polar cataract in this Japanese family is phenotypically and genetically distinct from previously mapped cataracts.