Figure 1.

Family 1, showing the S516R mutation in the transforming growth factor beta Induced (TGFBI) gene. A: Pedigree of the family. Filled boxes represent affected individuals. Open boxes represent unaffected individuals. Arrowhead indicates the proband. Filled circle with a slash indicates a deceased individual. B: Slit lamp photomicrograph of the affected individual. The representative clinical photograph shows the presence of discrete gray-white deposits in the right eye of the proband, with clear intervening stroma resembling granular corneal dystrophy. C: Partial nucleotide sequence of the transforming growth factor beta induced (TGFBI) gene. The chromatogram of the patient (P) is shown compared to a control (C). A heterozygous C>G substitution, marked by the arrowhead, is shown. The black box denotes the nucleotide that causes the missense mutation resulting in amino acid substitution of the Serine (S) at amino acid position 516 with Arginine (R). The partially dashed blue line at the top left of the chromatogram marks the intronic region, while the red line on the right marks the start of the exon. D: Protein modeling in S516R mutation showing the superimposition of S516R mutant (yellow) and wild type conformers (cyan). Only the mutant structures, where the deviations were observed, are shown in the figure. The conformational changes in the secondary structure elements are shown for amino acid residues 505–511 (A), 516–525 (B) and 544–550 (C). The changes observed in molecular interactions (Hydrogen bonds) are also marked by dashed lines.