title: CYP1B1 mutation profile of Iranian primary congenital glaucoma patients and associated haplotypes.
abstract: The mutation spectrum of CYP1B1 among 104 primary congenital glaucoma patients of the genetically heterogeneous Iranian population was investigated by sequencing. We also determined intragenic single nucleotide polymorphism (SNP) haplotypes associated with the mutations and compared these with haplotypes of other populations. Finally, the frequency distribution of the haplotypes was compared among primary congenital glaucoma patients with and without CYP1B1 mutations and normal controls. Genotype classification of six high-frequency SNPs was performed using the PHASE 2.0 software. CYP1B1 mutations in the Iranian patients were very heterogeneous. Nineteen nonconservative mutations associated with disease, and 10 variations not associated with disease were identified. Ten mutations and three variations not associated with disease were novel. The 13 novel variations make a notable contribution to the approximately 70 known variations in the gene. CYP1B1 mutations were identified in 70% of the patients. The four most common mutations were G61E, R368H, R390H, and R469W, which together constituted 76.2% of the CYP1B1 mutated alleles found. Six unique core SNP haplotypes were identified, four of which were common to the patients with and without CYP1B1 mutations and controls studied. Three SNP blocks determined the haplotypes. Comparison of haplotypes with those of other populations suggests a common origin for many of the mutations.
authors.affiliation: National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Chitsazian
authors.forename: Betsabeh Khoramian
authors.initials: BK
authors.lastname: Tusi
authors.forename: Elahe
authors.initials: E
authors.lastname: Elahi
authors.forename: Heidar Amini
authors.initials: HA
authors.lastname: Saroei
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Sanati
authors.forename: Shahin
authors.initials: S
authors.lastname: Yazdani
authors.forename: Mohammad
authors.initials: M
authors.lastname: Pakravan
authors.forename: Navid
authors.initials: N
authors.lastname: Nilforooshan
authors.forename: Yadollah
authors.initials: Y
authors.lastname: Eslami
authors.forename: Mohammad Ali Zare
authors.initials: MA
authors.lastname: Mehrjerdi
authors.forename: Reza
authors.initials: R
authors.lastname: Zareei
authors.forename: Mahmood
authors.initials: M
authors.lastname: Jabbarvand
authors.forename: Ali
authors.initials: A
authors.lastname: Abdolahi
authors.forename: Ali R
authors.initials: AR
authors.lastname: Lasheyee
authors.forename: Arash
authors.initials: A
authors.lastname: Etemadi
authors.forename: Behnaz
authors.initials: B
authors.lastname: Bayat
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sadeghi
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Banoei
authors.forename: Behnam
authors.initials: B
authors.lastname: Ghafarzadeh
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Rohani
authors.forename: Akram
authors.initials: A
authors.lastname: Rismanchian
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Thorstenson
authors.forename: Mansoor
authors.initials: M
authors.lastname: Sarfarazi
mesh_terms: D000595:Amino Acid Sequence; D001189:Aryl Hydrocarbon Hydroxylases; D016022:Case-Control Studies; D002675:Child, Preschool; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D008040:Genetic Linkage; D005901:Glaucoma / Q000151:congenital* / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007492:Iran; D008969:Molecular Sequence Data; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017386:Sequence Homology, Amino Acid
chemical_list: D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1