title: Mutation spectrum of CYP1B1 and MYOC genes in Korean patients with primary congenital glaucoma.
abstract: OBJECTIVE
  To elucidate the incidence of cytochrome P450 1B1 (CYP1B1) and myocillin (MYOC) mutations in Korean patients with primary congenital glaucoma (PCG).
  
  
  METHODS
  Genomic DNA was collected from peripheral blood of 85 unrelated Korean patients who were diagnosed as having PCG by standard ophthalmological examinations and screened for mutations in the CYP1B1 and MYOC genes by using bi-directional sequencing.
  
  
  RESULTS
  Among 85 patients with PCG, 22 patients (22/85; 25.9%) had either one (n=11) or two (n=11) mutant alleles of the CYP1B1 gene. Among 11 different CYP1B1 mutations identified, a frameshift mutation (c.970_971dupAT; p.T325SfsX104) was the most frequent mutant allele (6/33; 18.2%) while p.G329S and p.V419Gfs11X were novel. In the MYOC gene, two variants of unknown significance (p.L228S and p.E240G) were identified in two PCG patients (2/85; 2.4%), respectively. No patient had mutations in both genes.
  
  
  CONCLUSIONS
  Although CYP1B1 mutations are major causes of PCG in Korea, ~70% of PCG patients have neither CYP1B1 nor MYOC mutations suggesting a high degree of genetic heterogeneity. Furthermore, the fact that 11 out of 22 patients had only one mutant allele in the CYP1B1 gene necessitates further investigation for other genetic backgrounds underlying PCG.
authors.affiliation: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Wool
authors.initials: W
authors.lastname: Suh
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Park
authors.forename: Chan Yun
authors.initials: CY
authors.lastname: Kim
authors.forename: Ki Ho
authors.initials: KH
authors.lastname: Park
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kook
authors.forename: Yong Yeon
authors.initials: YY
authors.lastname: Kim
authors.forename: Chang-Sik
authors.initials: CS
authors.lastname: Kim
authors.forename: Chan Kee
authors.initials: CK
authors.lastname: Park
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Changwon
authors.initials: C
authors.lastname: Kee
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D005820:Genetic Testing; D005901:Glaucoma / Q000151:congenital / Q000208:ethnology / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008297:Male; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea / Q000453:epidemiology; D000099179:Myocilin
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D065633:Cytochrome P-450 CYP1B1; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin; C585496:CYP1B1 protein, human