title: Sequencing of the CHST6 gene in Czech macular corneal dystrophy patients supports the evidence of a founder mutation.
abstract: OBJECTIVE
  To characterise the role of the carbohydrate sulfotransferase gene (CHST6) in macular corneal dystrophy (MCD) in Czech patients.
  
  
  METHODS
  The coding region of the CHST6 gene was directly sequenced in 10 affected and five unaffected members from eight apparently unrelated MCD families. The type of MCD was determined by enzyme-linked immunosorbent assay of antigenic keratan sulfate (KS) in serum and by immunohistochemical staining of corneas with monoclonal anti-KS antibody.
  
  
  RESULTS
  The following changes in the coding sequence of the CHST6 gene were observed; homozygous mutation of c.1A>T (p.M1?); homozygous mutation c.599T>G (p.L200R); compound heterozygosity for c.599T>G and c.614G>A (p.R205Q); compound heterozygosity for c.494G>A (p.C165Y) and c.599T>G; heterozygous c.599T>G mutation and no other change in the coding sequence. One proband exhibited no changes. The pathogenic mutation c.599T>G (p.L200R) was in allelic association with the c.484C>G (p.R162G) polymorphism. Nine patients from seven families were of MCD type I including the subtype IA.
  
  
  CONCLUSIONS
  Four different CHST6 missense mutations, of which p.C165Y is novel, were identified. Allelic association of the c.[484C>G; 599T>G] in six probands out of eight, as well as occurrence of this particular allele in a heterozygous state in one healthy control individual, supports a common founder effect for MCD in the Czech Republic.
authors.affiliation: Division of Molecular Genetics, Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK. p.liskova@ucl.ac.uk
authors.forename: P
authors.initials: P
authors.lastname: Liskova
authors.forename: B
authors.initials: B
authors.lastname: Veraitch
authors.forename: K
authors.initials: K
authors.lastname: Jirsova
authors.forename: M
authors.initials: M
authors.lastname: Filipec
authors.forename: A
authors.initials: A
authors.lastname: Neuwirth
authors.forename: N D
authors.initials: ND
authors.lastname: Ebenezer
authors.forename: P G
authors.initials: PG
authors.lastname: Hysi
authors.forename: A J
authors.initials: AJ
authors.lastname: Hardcastle
authors.forename: S J
authors.initials: SJ
authors.lastname: Tuft
authors.forename: S S
authors.initials: SS
authors.lastname: Bhattacharya
mesh_terms: D001323:Autoantibodies / Q000032:analysis / Q000097:blood; D001483:Base Sequence; D003315:Cornea / Q000276:immunology; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000276:immunology; D018703:Founder Effect; D006801:Humans; D007632:Keratan Sulfate / Q000276:immunology; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D015238:Sulfotransferases / Q000235:genetics*; D000097811:Carbohydrate Sulfotransferases
chemical_list: D001323:Autoantibodies; D007632:Keratan Sulfate; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases