title: Identification of novel mutations in the carbohydrate sulfotransferase gene (CHST6) causing macular corneal dystrophy.
abstract: OBJECTIVE
  Macular corneal dystrophy (MCD) is a rare corneal dystrophy that is characterized by abnormal deposits in the corneal stroma, keratocytes, Descemet's membrane, and endothelium, accompanied by progressive clouding. It has been classified into three immunophenotypes--MCD types I, IA, and II--according to the serum level of sulfated keratan sulfate (KS) and immunoreactivity of the corneal tissue. Recently, mutations in a new carbohydrate sulfotransferase gene (CHST6) encoding corneal glucosamine N-acetyl-6-sulfotransferase (C-GlcNac-6-ST) have been identified as the cause of MCD. Mutation screening of the CHST6 gene has been undertaken to identify the underlying mutations in five unrelated British families with MCD.
  
  
  METHODS
  DNA was extracted from venous blood obtained from all participants, and the coding region of CHST6 was amplified by polymerase chain reaction (PCR). The PCR products were analyzed by direct sequencing and restriction enzyme digestion. Enzyme-linked immunosorbent assay (ELISA) was performed to assess the presence of KS in serum from the probands of MCD-affected families participating in the study.
  
  
  RESULTS
  Six novel missense mutations--four homozygous and two compound heterozygous--were identified in the CHST6 gene. The ELISA showed that the disease in all patients participating in the study was of MCD type I, including the subtype IA.
  
  
  CONCLUSIONS
  These novel mutations are thought to result in loss of corneal sulfotransferase function, which would account for the MCD phenotype.
authors.affiliation: Department of Molecular Genetics, Institute of Ophthalmology, London, United Kingdom. m_el_ashry@hotmail.com
authors.forename: Mohamed F
authors.initials: MF
authors.lastname: El-Ashry
authors.forename: Mai M
authors.initials: MM
authors.lastname: Abd El-Aziz
authors.forename: Simon
authors.initials: S
authors.lastname: Wilkins
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cheetham
authors.forename: Susan E
authors.initials: SE
authors.lastname: Wilkie
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Hardcastle
authors.forename: Stephanie
authors.initials: S
authors.lastname: Halford
authors.forename: Ahmed Y
authors.initials: AY
authors.lastname: Bayoumi
authors.forename: Linda A
authors.initials: LA
authors.lastname: Ficker
authors.forename: Stephen
authors.initials: S
authors.lastname: Tuft
authors.forename: Shomi S
authors.initials: SS
authors.lastname: Bhattacharya
authors.forename: Neil D
authors.initials: ND
authors.lastname: Ebenezer
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003315:Cornea / Q000201:enzymology* / Q000473:pathology; D003317:Corneal Dystrophies, Hereditary / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007632:Keratan Sulfate / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D015238:Sulfotransferases / Q000235:genetics*; D000097811:Carbohydrate Sulfotransferases
chemical_list: D017931:DNA Primers; D007632:Keratan Sulfate; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases