Macular corneal dystrophy type I and type II are caused by distinct mutations in a new sulphotransferase gene

Macular corneal dystrophy (MCD; MIM 217800) is an autosomal recessive hered itary disease in which progressive punctate opacities in the cornea result in bilateral loss of vision, eventually necessitating corneal transplantati on. MCD is classified into two subtypes. type I and type II, defined by the respective absence and presence of sulphated keratan sulphate in the patie nt serum, although both types have clinically indistinguishable phenotypes( 1,2). The gene responsible for MCD type I has been mapped to chromosome 16q 22, and that responsible for MCD type II may involve the same locus(3-5). H ere we identify a new carbohydrate sulphotransferase gene (CHST6). encoding an enzyme designated corneal N-acetylglucosamine-6-sulphotransferase (C-Gl cNAc6ST), within the critical region of MCD type I. In MCD type I. we ident ified several mutations that may lead to inactivation of C-GlcNAc6ST within the coding region of CHST6. In MCD type II, we found large deletions and/o r replacements caused by homologous recombination in the upstream region of CHST6. In situ hybridization analysis did not detect CHST6 transcripts in corneal epithelium in an MCD type II patient, suggesting that the mutations found in type II lead to loss of cornea-specific expression of CHST6.