title: Investigation of CYP1B1 mutations in Chinese patients with primary congenital glaucoma.
abstract: OBJECTIVE
  This study was conducted to investigate the mutation spectrum of the cytochrome P450 gene (CYP1B1) in Chinese patients with primary congenital glaucoma (PCG).
  
  
  METHODS
  The coding regions of CYP1B1 from 41 Chinese PCG patients were analyzed using polymerase chain reaction (PCR) and heteroduplex analysis-single strand conformation polymorphism (HA-SSCP) followed by subsequent cloning and bidirectional sequencing. New variants were confirmed by restriction fragment length polymorphism (RFLP) analysis in 80 normal Chinese controls.
  
  
  RESULTS
  Six distinct mutations, four of which are novel, were identified in 14.6% (6/41) of all patients. The CYP1B1 mutations in two patients were homozygous, and the other four patients were compound heterozygous. Beyond the four novel mutations (g.4531_4552del22bp, g.4633delC, p.S336Y, and p.I471S), two reported missense mutations (R469W and R390H) were also identified. The missense mutation, R390H, was involved in 9.8% (4/41) of patients in our study. None of the novel mutations was observed in any of the 80 controls.
  
  
  CONCLUSIONS
  Our results support the premise that CYP1B1 is a major gene for PCG, appearing to be responsible for the disease in roughly one in six Chinese PCG patients. The R390H mutation was identified as a predominant CYP1B1 allele among the Chinese PCG patients in our study. This observation emphasizes the importance of mutational screening of CYP1B1, especially for the R390H mutation in Chinese patients.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.forename: Xiangming
authors.initials: X
authors.lastname: Guo
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Huangxuan
authors.initials: H
authors.lastname: Shen
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Jia
authors.forename: Xueshan
authors.initials: X
authors.lastname: Xiao
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Li
authors.forename: Shaohua
authors.initials: S
authors.lastname: Fang
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D001120:Arginine; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D005901:Glaucoma / Q000151:congenital* / Q000235:genetics*; D006579:Heterozygote; D006639:Histidine; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D055815:Young Adult
chemical_list: D006639:Histidine; D001120:Arginine; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1