title: Macular corneal dystrophy type I and type II are caused by distinct mutations in a new sulphotransferase gene.
abstract: Macular corneal dystrophy (MCD; MIM 217800) is an autosomal recessive hereditary disease in which progressive punctate opacities in the cornea result in bilateral loss of vision, eventually necessitating corneal transplantation. MCD is classified into two subtypes, type I and type II, defined by the respective absence and presence of sulphated keratan sulphate in the patient serum, although both types have clinically indistinguishable phenotypes. The gene responsible for MCD type I has been mapped to chromosome 16q22, and that responsible for MCD type II may involve the same locus. Here we identify a new carbohydrate sulphotransferase gene (CHST6), encoding an enzyme designated corneal N-acetylglucosamine-6-sulphotransferase (C-GlcNAc6ST), within the critical region of MCD type I. In MCD type I, we identified 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/or 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.
authors.affiliation: Glycobiology Program, The Burnham Institute, La Jolla, California, USA.
authors.forename: T O
authors.initials: TO
authors.lastname: Akama
authors.forename: K
authors.initials: K
authors.lastname: Nishida
authors.forename: J
authors.initials: J
authors.lastname: Nakayama
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Ozaki
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: A
authors.initials: A
authors.lastname: Dota
authors.forename: S
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: N
authors.initials: N
authors.lastname: Maeda
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Fujiwara
authors.forename: E J
authors.initials: EJ
authors.lastname: Thonar
authors.forename: Y
authors.initials: Y
authors.lastname: Shimomura
authors.forename: S
authors.initials: S
authors.lastname: Kinoshita
authors.forename: A
authors.initials: A
authors.lastname: Tanigami
authors.forename: M N
authors.initials: MN
authors.lastname: Fukuda
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D003317:Corneal Dystrophies, Hereditary / Q000145:classification / Q000201:enzymology / Q000235:genetics*; D020224:Expressed Sequence Tags; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007632:Keratan Sulfate / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015238:Sulfotransferases / Q000737:chemistry / Q000235:genetics*; D000097811:Carbohydrate Sulfotransferases
chemical_list: D005819:Genetic Markers; D007632:Keratan Sulfate; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases