title: Identification of four novel cytochrome P4501B1 mutations (p.I94X, p.H279D, p.Q340H, and p.K433K) in primary congenital glaucoma patients.
abstract: OBJECTIVE
  Primary congenital glaucoma (PCG) is an autosomal recessive eye disorder that is postulated to result from developmental defects in the anterior eye segment. Mutations in the cytochrome P4501B1 (CYP1B1) gene are a predominant cause of congenital glaucoma. In this study we identify CYP1B1 mutations in PCG patients.
  
  
  METHODS
  Twenty-three unrelated PCG patients and 50 healthy controls were enrolled in the study. CYP1B1 was screened for mutations by PCR and DNA sequencing.
  
  
  RESULTS
  DNA sequencing revealed a total of 15 mutations. Out of these, four (p.I94X, p.H279D, p.Q340H, and p.K433K) were novel mutations and five were known pathogenic mutations. Five coding single nucleotide polymorphisms and one intronic single nucleotide polymorphism (rs2617266) were also found. Truncating mutations (p.I94X and p.R355X) were associated with the most severe disease phenotype. It is possible that patients with two null alleles with no catalytic activity may present with a more severe phenotype of the disease compared to patients with one null allele (heterozygous). The disease phenotype of patients with CYP1B1 mutations was more severe compared with the clinical phenotype of patients negative for CYP1B1 mutations.
  
  
  CONCLUSIONS
  Mutations in CYP1B1 are a major cause for PCG in our patients. Identifying mutations in subjects at risk of developing glaucoma, particularly among relatives of PCG patients, is of clinical significance. These developments may help in reducing the disease frequency in familial cases. Such studies will be of benefit in the identification of pathogenic mutations in different populations and will enable us to develop simple and rapid diagnostic tests for analyzing such cases.
authors.affiliation: Laboratory For Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Tanwar
authors.forename: Tanuj
authors.initials: T
authors.lastname: Dada
authors.forename: Ramanjit
authors.initials: R
authors.lastname: Sihota
authors.forename: Rima
authors.initials: R
authors.lastname: Dada
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005901:Glaucoma / Q000151:congenital* / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D003062:Codon; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1