Twelve Novel Mutations in the CHST6 Gene Result in Macular Corneal Dystrophy

Abstract

Abstract: : Purpose: Identification of mutations in the CHST6 gene in fifteen patients from eleven unrelated families affected with recessive macular corneal dystrophy. 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 mutations. 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 MCD patients combined with those reported from previous studies indicated CHST6 mutational heterogeneity. The characterization, here, of nonsense mutations is in keeping with the fact that MCD results from loss of function of the CHST6 protein product.

Keywords: cornea: basic science • genetics • clinical (human) or epidemiologic studies: pre