Truncating mutations in the carbohydrate sulfotransferase 6 gene (CHST6) result in macular corneal dystrophy.

PURPOSE Identification of mutations in the CHST6 gene in 15 patients from 11 unrelated families affected with recessive macular corneal dystrophy (MCD). METHODS Genomic DNA was extracted from peripheral blood leukocytes of the affected patients and their healthy family members, and the mutational status of the CHST6 gene was determined for each patient by a PCR-sequencing approach. Serum concentrations of antigenic keratan sulfate for each proband were determined by ELISA. RESULTS ELISA indicated that all affected patients, except one, were of MCD type I or IA. Fourteen distinct mutations were identified within the CHST6 coding region: 2 nonsense, 2 frameshift, and 10 missense. Of these, 12 were novel, and a nonsense mutation in the homozygous state is reported for the first time. CONCLUSIONS These molecular results in French patients with MCD combined with those reported in previous studies indicated CHST6 mutational heterogeneity. The characterization herein of nonsense mutations is in keeping with the fact that MCD results from loss of function of the CHST6 protein product.