title: Macular corneal dystrophy types I and II are caused by distinct mutations in the CHST6 gene in Iceland.
abstract: OBJECTIVE
  To identify CHST6 mutations in five additional Icelandic cases of macular corneal dystrophy (MCD) type I and in four families with MCD type II from Iceland.
  
  
  METHODS
  Genomic DNA was extracted from blood leukocytes of patients with MCD, their healthy family members, and from control individuals. CHST6 mutations were determined by PCR-sequencing. Immunophenotypes of MCD were determined by measuring antigenic keratan sulfate (AgKS) levels in serum and by an immunohistochemical study on corneal tissue.
  
  
  RESULTS
  Five additional cases of MCD type I and four families with MCD type II from Iceland were studied. A homozygous p.A128V mutation in the coding region of the CHST6 gene was identified in four of the five MCD type I cases. The other person with MCD type I was a compound heterozygote for p.A128V and a frameshift p.V6fs resulting from a 10-base pair insertion (c.15_16insATGCTGTGCG). Four of five individuals with MCD type II were compound heterozygotes for p.A128V and p.V329L, thus sharing the same p.A128V mutation as MCD type I. One patient with MCD type II was homozygous for p.V329L. The p.V329L mutation was only found in MCD type II patients. An analysis of the upstream region of CHST6 disclosed no upstream deletion or replacements in Icelandic patients with MCD type II.
  
  
  CONCLUSIONS
  The findings fit the haplotype analysis that we reported previously in Icelandic MCD families and indicate that different mutations in CHST6 cause MCD type I and type II in Iceland.
authors.affiliation: Beijing Tongren Eye Center, Capital University of Medical Sciences, Beijing, China. nliu001@gmail.com <nliu001@gmail.com>
authors.forename: Ning-Pu
authors.initials: NP
authors.lastname: Liu
authors.forename: Clayton F
authors.initials: CF
authors.lastname: Smith
authors.forename: Brandy L
authors.initials: BL
authors.lastname: Bowling
authors.forename: Fridbert
authors.initials: F
authors.lastname: Jonasson
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Klintworth
mesh_terms: D000409:Alanine; D003317:Corneal Dystrophies, Hereditary / Q000145:classification* / Q000235:genetics*; D004251:DNA Transposable Elements; D005260:Female; D016368:Frameshift Mutation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007055:Iceland; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007930:Leucine; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D015238:Sulfotransferases / Q000235:genetics*; D014633:Valine; D000097811:Carbohydrate Sulfotransferases
chemical_list: D000409:Alanine; D004251:DNA Transposable Elements; D007930:Leucine; D015238:Sulfotransferases; D014633:Valine; D000097811:Carbohydrate Sulfotransferases