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Mutations in the BIGH3 gene on chromosome 5q31 cause 4 distinct autosomal dominant human cornea diseases characterized by accumulation of corneal deposits in a progressive fashion and in time by loss of vision. A specific recurrent missense mutation for each type of dystrophy is in 10 independently ascertained families. Genotype analysis with microsatellite markers around BIGH3 has been carried out for the 10 families and in 5 families reported in the past. New data imply that R555W, H124H and R124C mutations were independent in a number of ethnic groups. Apparently the mutations don't reflect a putative founder effect. The specific importance of the R124 and R555 amino acids in the pathogenesis of autosomal dominant corneal dystrophies linked to 5p has been confirmed.

Mutations in the BIGH3 gene on chromosome 5q31 cause four distinct autosomal dominant diseases of the human cornea: granular (Groenouw type I), Reis-Bücklers, lattice type I, and Avellino corneal dystrophies. All four diseases are characterized by both progressive accumulation of corneal deposits and eventual loss of vision. We have identified a specific recurrent missense mutation for each type of dystrophy, in 10 independently ascertained families. Genotype analysis with microsatellite markers surrounding the BIGH3 locus was performed in these 10 families and in 5 families reported previously. The affected haplotype could be determined in 10 of the 15 families and was different in each family. These data indicate that R555W, R124C, and R124H mutations occurred independently in several ethnic groups and that these mutations do not reflect a putative founder effect. Furthermore, this study confirms the specific importance of the R124 and R555 amino acids in the pathogenesis of autosomal dominant corneal dystrophies linked to 5q.