title: CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma.
abstract: BACKGROUND
  Primary open-angle glaucoma (POAG) is a leading cause of visual impairment worldwide and a complex genetic disorder that affects mostly adults. Mutations in the MYOCILIN (MYOC) and OPTINEURIN genes account for rare forms with a Mendelian inheritance and for <5% of all POAG cases. The CYP1B1 gene, a member of the cytochrome P450 gene family, is a major cause of primary congenital glaucoma (PCG), a rare and severely blinding disease with recessive inheritance. However, CYP1B1 mutations have also been associated with cases of juvenile-onset glaucoma in some PCG families or shown to modify the age of onset of glaucoma linked to a MYOC mutation in a large family.
  
  
  OBJECTIVE
  To investigate the role of CYP1B1 mutations in POAG predisposition, irrespective of the presence of a MYOC mutation.
  
  
  METHODS
  CYP1B1 coding region variation was characterised by denaturing high performance liquid chromatography (DHPLC) and sequencing in 236 unrelated French Caucasian POAG patients and 47 population-matched controls.
  
  
  RESULTS
  Eleven (4.6%) patients carried one or two mutated CYP1B1 gene(s) and no MYOC mutation. They showed juvenile or middle-age onset of disease (median age at diagnosis, 40 years, range 13-52), significantly earlier than in non-carrier patients. Apart from one, all mutations detected in POAG patients were previously associated with PCG.
  
  
  CONCLUSIONS
  CYP1B1 mutations might pose a significant risk for early-onset POAG and might also modify glaucoma phenotype in patients who do not carry a MYOC mutation.
authors.affiliation: INSERM U580, Hôpital Necker, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Melki
authors.forename: E
authors.initials: E
authors.lastname: Colomb
authors.forename: N
authors.initials: N
authors.lastname: Lefort
authors.forename: A P
authors.initials: AP
authors.lastname: Brézin
authors.forename: H-J
authors.initials: HJ
authors.lastname: Garchon
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002648:Child; D065633:Cytochrome P-450 CYP1B1; D004252:DNA Mutational Analysis; D005260:Female; D005602:France; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1