Figure 3. Characterization of a new coding variant Arg721Gln in exon 13.

(A) An example electropherogram of the coding strand is displayed for an affected and an unaffected individual, with the arrow marking the variant. Individuals with disease were heterozygotes (CAG) for Gln/Arg while unaffected individuals were homozygotes for Arg/Arg (CGG). (B) A large family with cortical cataract was examined and the co-segregation of Arg721Gln with cortical cataract determined. Two members (3-1 and 3-2) and one marry-in (3-3) were GG (Arg/Arg) but have cortical cataract, suggesting phenocopies. Symbols filled with black or gray represent those affected with severe (≥25% of the lens affected) or moderate (5%≤score<25%) cortical cataract, respectively. In the parent generation, all heterozygotes for the Arg721Gln variant developed severe cortical cataract or have had cataract surgery. However, this variant has age dependent penetrance, as individuals who developed severe disease are older (e.g. individual 3-4 who is 80 years old). Individuals in the offspring generation who are at risk may not have developed full-fledged cortical cataract (e.g. 4-1 who is less than age 65 with moderate cataract, or 4-2 who is a carrier but remains free of disease at age 63).