Figure 3. Detection of two pathogenic mutations (R124C and R555W) and two DNA polymorphisms (H482H and F540F) of the TGFBI gene in two Spanish families with autosomal dominant corneal dystrophy

Representative DNA sequences around codons 124 (exon 4; A, top panel) and 555 (exon 12; B, top panel) show two heterozygous C>T transitions detected in affected members of the families CD1 and CD2, respectively. The nucleotide substitutions at codons 124 (c.370) and 555 (c.1663) result in arginine to cysteine (R124C) and arginine to tryptophan changes (R555W), respectively. Representative DNA sequences around codons 482 and 540 show two the heterozygous C>T transitions identified in members of the family CD2 (C and D, top panels). The nucleotide substitutions at codons 482 (c.1551) and 540 (c.1725) result in the H482H and F540F polymorphisms, respectively. The H482H polymorphism has been identified in this study for the first time. The R124C and R555W mutations segregated with the disease phenotype and were not detected in unaffected subjects. Control electropherograms are shown for comparison purposes (A-D, bottom panel). The arrows highlight the position of nucleotide substitutions.