An autosomal dominant anterior polar cataract is linked to the short arm of human chromosome 17

Purpose. Inherited cataract is a clinically and genetically heterogeneous disease that is most often transmitted as a congenital autosomal dominant trait. Here we have used genetic linkage analysis to map the gene for an autosomal dominant anterior polar cataract in a four-generation English pedigree that is solely affected with this type of lens opacity. Methods. Genomic DNA was extracted from blood samples taken with informed consent from 28 pedigree members. Genethon microsatellite markers were amplified using the polymerase chain reaction and 5′-end labeled primers, then separated on sequencing gels and detected by autoradiography. Genetic linkage analysis was performed using the LINKAGE package of programs. Results. After exclusion of several candidate loci for cataract, we obtained significant positive lod scores (Z), at a recombination distance θ = 0.05, for markers D17S849 (Z = 4.01) and D17S796 (Z = 4.17) on chromosome 17p. Multipoint analysis gave a maximum lod score of 5.2 @ θ_max = 0.06 between these two markers. From haplotype analysis, this cataract locus lies in the 14 cM interval between markers D17S849 and D17S796 toward the telomeric end of 17p. Conclusions. These data provide the first genetic mapping of a non-syndromic autosomal dominant anterior polar cataract. The new cataract locus is both clinically and genetically distinct from two other cataract loci on chromosome 17q and brings the current number of genetically mapped loci for autosomal dominant cataract to seven.