Purpose: To identify underlying genetic defects in the carbohydrate sulfotransferase-6 (CHST6) gene in North Indian patients with macular corneal dystrophy (MCD).
Methods: 30 clinically diagnosed MCD patients from 21 families and 50 healthy normal controls were recruited in the study. Detailed clinical evaluation in the patients was undertaken followed by histopathology and ultrastructural studies in corneal tissues. DNA from blood samples was amplified for the CHST6 coding and upstream region followed by direct sequencing and in silico analysis.
Results: We identified pathogenic mutations in 17 patients from 11 families. Of these 4 were novel (p.Ser54Tyr, p.Gln58Arg, p.Leu59His and p.Leu293Phe), 2 were previously reported (Arg93His and Glu274Lys) homozygous, 1 heterozygous stop codon (p.Trp123X) and 2 compound heterozygous (p.Arg93His + p.Arg97Pro; p.Leu22Arg + p.Gln58X) mutations. A missense single-nucleotide polymorphism was also identified in 11 patients. The novel mutations were conserved as shown by in silico analysis. Thirteen patients did not show any pathogenic CHST6 changes.
Conclusions: This is the first report on molecular analysis of MCD in North Indian patients. All cases could not be explained by mutations in CHST6, suggesting that MCD may result from other changes in the regulatory elements of CHST6 or from genetic heterogeneity.
Copyright © 2012 S. Karger AG, Basel.