title: Novel mutations of CHST6 in Iranian patients with macular corneal dystrophy.
abstract: OBJECTIVE
  To characterize mutations within the carbohydrate sulfotransferase 6 (CHST6) gene in Iranian subjects from 12 families with macular corneal dystrophy (MCD).
  
  
  METHODS
  Genomic DNA was extracted from peripheral blood of 20 affected patients and 60 healthy volunteers followed by polymerase chain reaction (PCR) and direct sequencing of the CHST6 coding region. The observed nucleotide sequences were then compared with those found by investigators in other populations with MCD and in the controls.
  
  
  RESULTS
  Analysis of CHST6 revealed 11 different mutations. These mutations were comprised of six novel missense mutations (p.F55L, p.P132L, p.S136G, p.C149Y, p.D203Y, and p.H249R), one novel nonsense mutation (p.S48X), one novel frame shift (after P297), and three previously reported missense mutations (p.P31L, p.C165Y, and p.R127C). The majority of the detected MCD mutations are located in the binding sites or the binding pocket, except the p.P31L and p.H249R mutations.
  
  
  CONCLUSIONS
  Nucleotide changes within the coding region of CHST6 are predicted to significantly alter the encoded sulfotransferase within the evolutionary conserved sequences. Our findings show that CHST6 mutations are responsible for the pathogenesis of MCD in Iranian patients. Moreover, the observation that some cases of MCD cannot be explained by mutations in the coding region of CHST6 suggests that MCD may result from possible upstream rearrangements in the CHST6 genomic region.
authors.affiliation: Department of Biology, University of Guilan Medical Science, Rasht, Iran. akbaribirgani_sh@yahoo.com
authors.forename: Shiva Akbari
authors.initials: SA
authors.lastname: Birgani
authors.forename: Zivar
authors.initials: Z
authors.lastname: Salehi
authors.forename: Masoud
authors.initials: M
authors.lastname: Houshmand
authors.forename: Mohamad Javad
authors.initials: MJ
authors.lastname: Mohamadi
authors.forename: Leila Azizade
authors.initials: LA
authors.lastname: Promehr
authors.forename: Zahra
authors.initials: Z
authors.lastname: Mozafarzadeh
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D016022:Case-Control Studies; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D007492:Iran; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D015238:Sulfotransferases / Q000737:chemistry / Q000235:genetics*; D000097811:Carbohydrate Sulfotransferases
chemical_list: D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases