title: Molecular analysis of the CHST6 gene in Korean patients with macular corneal dystrophy: Identification of three novel mutations.
abstract: OBJECTIVE
  To identify the underlying genetic defect in Korean patients with macular corneal dystrophy (MCD).
  
  
  METHODS
  Genomic DNA was isolated from peripheral blood leukocytes of seven patients from six unrelated families with MCD (three men and four women). Polymerase chain reaction was performed for coding regions of the carbohydrate sulfotransferase (CHST6), gene followed by bidirectional sequencing. Targeted mutational analysis (exons 4, 11-12, 14) of the transforming growth factor, beta-induced (TGFBI) gene was performed for all patients.
  
  
  RESULTS
  All seven patients were found to have compound heterozygous mutations in the CHST6 gene. In addition to six previously reported mutations, c.95C>A (p.Ser32*), c.521A>G (p.Lys174Arg), c.557C>G (p.Pro186Arg), c.613C>T (p.Arg205Trp), c.820G>A (p.Glu274Lys), and c.1072T>C (p.Tyr358His), three novel mutations were identified in this study, including two missense mutations, c.353C>T (p.Ser118Phe) and c.922C>T (p.His308Tyr), and one frameshift mutation, c.786delC (p.L264Cfs*117). Among the three novel mutations, only the c.353C>T mutation had been reported in the Exon Aggregation Consortium database at an extremely low frequency of 0.00005072. In addition, these three novel mutations were absent from controls in 1,000 genomes, dbSNP, and the TIARA genome database, which is a Korean personal genome database. The most frequent mutation was c.613C>T (p.Arg205Trp), revealed in four unrelated Korean families, which has not previously been reported in other populations. No mutations were detected in the TGFBI gene.
  
  
  CONCLUSIONS
  This is the first report on genetic analysis of Korean MCD patients. Three novel and six previously reported disease-causing CHST6 mutations were identified, which expands the mutational spectrum of MCD.
authors.affiliation: Department of Ophthalmology and Visual Science, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Shin Hae
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Ophthalmology and Visual Science, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Ye Jin
authors.initials: YJ
authors.lastname: Ahn
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Seoul St, Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Chae
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Seoul St, Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Yonggoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology and Visual Science, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Man Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Seoul St, Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Myungshin
authors.initials: M
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D001483:Base Sequence; D016022:Case-Control Studies; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D003317:Corneal Dystrophies, Hereditary / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D030541:Databases, Genetic; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D015238:Sulfotransferases / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000097811:Carbohydrate Sulfotransferases; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D015238:Sulfotransferases; D016212:Transforming Growth Factor beta; D000097811:Carbohydrate Sulfotransferases; D000099222:betaIG-H3 Protein