Investigation of TGFBI (transforming growth factor beta-induced) Gene Mutations in Families with Granular Corneal Dystrophy Type 1 in the Konya Region.

OBJECTIVES

Granular corneal dystrophies (GCD) are characterized by small, discrete, sharp-edged, grayish-white opacities in the corneal stroma. Among the genes responsible for the development of GCD, the most strongly related gene is transforming growth factor beta-induced (), located in the 5q31.1 locus. Studies show that R124H in exon 4 and R555W in exon 12 are hot-spot mutations in the gene that lead to GCD development. In this study, we aimed to investigate these two hot-spot mutations in exons 4 and 12 of the gene and other possible mutations in the same regions, which code important functional regions of the protein, in Turkish families with GCD and to determine the relationship between the mutations and disease and related phenotypes.

MATERIALS AND METHODS

The study included 16 individuals diagnosed with GCD type 1 (GCD1), 11 of these patients' healthy relatives, and 28 unrelated healthy individuals. DNA was obtained from peripheral blood samples taken from each individual and polymerase chain reaction was used to amplify target gene regions. Genotyping studies were done by sequence analysis.

RESULTS

The R124S mutation in exon 4 of was not detected in the patients or healthy individuals in our study. However, all individuals diagnosed as having GCD1 were found to be heterozygous carriers of the R555W mutation in exon 12 of . This mutation was not detected in healthy family members or control individuals unrelated to these families. In addition, we detected the silent mutation F540F in exon 12 and c.32924 G>A substitution in an intronic region of the gene in a few patients and healthy individuals.

CONCLUSION

Our study strongly supports the association of GCD1 with R555W mutation in exon 12 region of the gene, as reported in the literature.