title: Novel cytochrome P450 1B1 (CYP1B1) mutations in patients with primary congenital glaucoma in France.
abstract: The CYP1B1 gene (GenBank: U56438), a member of the cytochrome P450 gene family, has been shown to be mutated in patients with primary congenital glaucoma (PCG), a rare but severely blinding form of glaucoma. Here, we have investigated CYP1B1 mutations in 31 unrelated French PCG patients. Mutations were found in 15 (48%) patients. Six of these mutations were novel. One, g.3979delA, caused a frameshift followed by a stop codon at residue 59. Two mutations, g.4547C>T (p.Q248X) and g.8167C>T (p.R444X), created a stop codon. Three other mutations, g.4499G>C (p.G232R), g.8033T>G (p.I399S), (p.N423Y), induced a significant amino acid change. Seven patients, who were of French descent, were compound heterozygotes. Six patients, whose families came from North Africa or from Portugal, carried a homozygous mutation reflecting their geographic origin. Intriguingly, one mutation, p.E229K, was present in heterozygous state in two unrelated patients. All together, these findings demonstrate the major role and the diversity of CYP1B1 mutations in French PCG patients.
authors.affiliation: INSERM U580, Paris, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Colomb
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.forename: Henri-Jean
authors.initials: HJ
authors.lastname: Garchon
mesh_terms: D000595:Amino Acid Sequence; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D005602:France; D005901:Glaucoma / Q000151:congenital / Q000201:enzymology / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D017386:Sequence Homology, Amino Acid
chemical_list: D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1