title: Novel mutations in the CHST6 gene associated with macular corneal dystrophy in southern India.
abstract: OBJECTIVE
  To further characterize the role of the carbohydrate sulfotransferase (CHST6) gene in macular corneal dystrophy (MCD) through identification of causative mutations in a cohort of affected patients from southern India.
  
  
  METHODS
  Genomic DNA was extracted from buccal epithelium of 75 patients (51 families) with MCD, 33 unaffected relatives, and 48 healthy volunteers. The coding region of the CHST6 gene was evaluated by means of polymerase chain reaction amplification and direct sequencing. Subtyping of MCD into types I and II was performed by measuring serum levels of antigenic keratan sulfate.
  
  
  RESULTS
  Seventy patients were classified as having type I MCD, and 5 patients as having type II MCD. Analysis of the CHST6 coding region in patients with type I MCD identified 11 homozygous missense mutations (Leu22Arg, His42Tyr, Arg50Cys, Arg50Leu, Ser53Leu, Arg97Pro, Cys102Tyr, Arg127Cys, Arg205Gln, His249Pro, and Glu274Lys), 2 compound heterozygous missense mutations (Arg93His and Ala206Thr), 5 homozygous deletion mutations (delCG707-708, delC890, delA1237, del1748-1770, and delORF), and 2 homozygous replacement mutations (ACCTAC 1273 GGT, and GCG 1304 AT). One patient with type II MCD was heterozygous for the C890 deletion mutation, whereas 4 possessed no CHST6 coding region mutations.
  
  
  CONCLUSIONS
  A variety of previously unreported mutations in the coding region of the CHST6 gene are associated with type I MCD in a cohort of patients in southern India.
  
  
  CONCLUSIONS
  An improved understanding of the genetic basis of MCD allows for earlier, more accurate diagnosis of affected individuals, and may provide the foundation for the development of novel disease treatments.
authors: Francis I. Proctor Foundation and the Department of Ophthalmology, University of California-San Francisco, 94143-0944, USA.
authors: John F
authors: JF
authors: Warren
authors: Anthony J
authors: AJ
authors: Aldave
authors: M
authors: M
authors: Srinivasan
authors: Eugene J
authors: EJ
authors: Thonar
authors: Abha B
authors: AB
authors: Kumar
authors: Vicky
authors: V
authors: Cevallos
authors: John P
authors: JP
authors: Whitcher
authors: Todd P
authors: TP
authors: Margolis
mesh_terms: D003317:Corneal Dystrophies, Hereditary / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D007194:India; D007632:Keratan Sulfate / Q000097:blood; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015238:Sulfotransferases / Q000235:genetics*; D000097811:Carbohydrate Sulfotransferases
chemical_list: D007632:Keratan Sulfate; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases