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 describ e here an autosomal dominant polymorphic congenital cataract (PCC) whi ch is characterised by wide variations in phenotype of nonnuclear lens opacities, even among affected members of the same family. PCC famili es included a large, unique pedigree (254 members, 103 affected indivi duals), and genetic linkage was conducted using a variety of polymorph ic markers. Evidence for linkage was found for chromosome 2q33-35 with PCC mapping near D2S72 and TNP1. A tri-nucleotide microsatellite mark er for gamma-crystallin B gene (CRYG1) was found to co-segregate with PCC and yielded a maximum lod score of 10.62 at (theta = 0). A multipo int analysis demonstrated that the most probable location of the PCC g ene was within an 8 cM genetic interval containing the gamma-crystalli n gene cluster. These data provide strong evidence of the existence of an autosomal dominant mutation for PCC in or near the gamma-crystalli n gene cluster. This defect is characterised by complete penetrance bu t variable expression of the cataract phenotype. Our study also sugges ts that non-nuclear human cataracts might be caused by some abnormalit y in gamma-crystallin genes.