Linkage of polymorphic congenital cataract to the gamma-crystallin gene locus on human chromosome 2q33-35

Cataract is one of the major causes of blindness in humans. We describehere an autosomal dominant polymorphic congenital cataract (PCC) which ischaracterised by wide variations in phenotype of non-nuclear lensopacities, even among affected members of the same family. PCC familiesincluded a large, unique pedigree (254 members, 103 affected individuals),and genetic linkage was conducted using a variety of polymorphic markers.Evidence for linkage was found for chromosome 2q33- 35 with PCC mappingnear D2S72 and TNP1. A tri-nucleotide microsatellite marker forgamma-crystallin B gene (CRYG1) was found to co-segregate with PCC andyielded a maximum lod score of 10.62 at (theta = 0). A multipoint analysisdemonstrated that the most probable location of the PCC gene was within an8 cM genetic interval containing the gamma-crystallin gene cluster. Thesedata provide strong evidence of the existence of an autosomal dominantmutation for PCC in or near the gamma-crystallin gene cluster. This defectis characterised by complete penetrance but variable expression of thecataract phenotype. Our study also suggests that non-nuclear humancataracts might be caused by some abnormality in gamma-crystallin genes.