Published online before print May 18, 2007

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Copyright © 2007 American Society for Investigative Pathology
Journal of Molecular Diagnostics, doi:10.2353/jmoldx.2007.060157

Accepted for publication February 7, 2007.

Article

CYP1B1 Mutation Profile of Iranian Primary Congenital Glaucoma Patients and Associated Haplotypes

Fereshteh Chitsazian^*, Betsabeh Khoramian Tusi^*, Elahe Elahi^*@, Heidar Amini Saroei, Mohammad H. Sanati^*, Shahin Yazdani^¶, Mohammad Pakravan^¶, Navid Nilforooshan^||, Yadollah Eslami, Mohammad Ali Zare Mehrjerdi, Reza Zareei, Mahmood Jabbarvand, Ali Abdolahi, Ali R. Lasheyee, Arash Etemadi, Behnaz Bayat^*, Mehdi Sadeghi^*, Mohammad M. Banoei^*, Behnam Ghafarzadeh^**, Mohammad R. Rohani^**, Akram Rismanchian, Yvonne Thorstenson, and Mansoor Sarfarazi

From the National Institute for Genetic Engineering and Biotechnology,* Tehran, Iran; the Department of Biological Sciences and the Bioinformatics Center, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; the Department of Ophthalmology, Farabi Eye Research Center, Tehran University of Medical Sciences, Tehran, Iran; the Ophthalmic Research Center,^¶ Shaheed Beheshti University of Medical Sciences, Tehran, Iran; the Department of Ophthalmology,^|| Iran University of Medical Sciences, Hazrat Rasool Hospital, Tehran, Iran; the Al-Zahra Ophthalmology Center,** Zahedan University of Medical Sciences, Zahedan, Iran; Esfahan Farabi Hospital, Esfahan University of Medical Sciences, Esfahan, Iran; DNA Variation and Function Group, Stanford Genome Technology Center, Stanford University, Palo Alto, California; and the Molecular Ophthalmic Genetics Laboratory, University of Connecticut Health Center, Farmington, Connecticut

^@ To whom correspondence should be addressed. E-mail: elahe.elahi{at}acnet.ir.

	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 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.