CYP1B1 mutation profile of Iranian primary congenital glaucoma patients and associated haplotypes.
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.
Chitsazian
Fereshteh
F
National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.
Tusi
Betsabeh Khoramian
BK
Elahi
Elahe
E
Saroei
Heidar Amini
HA
Sanati
Mohammad H
MH
Yazdani
Shahin
S
Pakravan
Mohammad
M
Nilforooshan
Navid
N
Eslami
Yadollah
Y
Mehrjerdi
Mohammad Ali Zare
MA
Zareei
Reza
R
Jabbarvand
Mahmood
M
Abdolahi
Ali
A
Lasheyee
Ali R
AR
Etemadi
Arash
A
Bayat
Behnaz
B
Sadeghi
Mehdi
M
Banoei
Mohammad M
MM
Ghafarzadeh
Behnam
B
Rohani
Mohammad R
MR
Rismanchian
Akram
A
Thorstenson
Yvonne
Y
Sarfarazi
Mansoor
M
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
D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1