A Haplotype Framework for Cystic Fibrosis Mutations in Iran

Abstract

This is the first comprehensive profile of cystic fibrosis transmembrane conductance regulator (CFTR) mutations and their corresponding haplotypes in the Iranian population. All of the 27 CFTR exons of 60 unrelated Iranian CF patients were sequenced to identify diseasecausing mutations. Eleven core haplotypes of CFTR were identified by genotyping six high-frequency simple nucleotide polymorphisms. The carrier frequency of 2.5 in 100 (1 in 40) was estimated from the frequency of heterozygous patients and suggests that contrary to popular belief, cystic fibrosis may be a common, underdiagnosed disease in Iran. A heterogeneous mutation spectrum was observed at the CFTR locus in 60 cystic fibrosis (CF) patients from Iran. Twenty putative disease-causing mutations were identified on 64 (53%) of the 120 chromosomes. The five most common Iranian mutations together represented 37% of the expected mutated alleles. The most frequent mutation, ⌬F508 (p.F508del), represented only 16% of the expected mutated alleles. The next most frequent mutations were c.1677del2 (p.515fs) at 7.5%, c.4041C>G (p.N1303K) at 5.6%, c.2183AA>G (p.684fs) at 5%, and c.3661A>T (p.K1177X) at 2.5%. Three of the five most frequent Iranian mutations are not included in a commonly used panel of CF mutations, underscoring the importance of identifying geographic-specific mutations in this population.

Poly Thymidine Polymorphism and Cystic Fibrosis in a Non-Caucasian Population

“…In the few studies performed in Iranian CF patients, various mutations were reported in CFTR gene. p.Phe508del is the most frequent mutation reported in Iran representing nearly 16% to 20% of mutations [14,18,20,36]. In this study the linkage between p.Phe508del mutation and polyT polymorphism was investigated.…”

“…Epithelial cells disorder is a dominant event in CF disease [13], causing a de-fect in transportation of electrolytes, water and other solutions from the cell membrane, leading to many different clinical symptoms such as lung infections, pancreas insufficiency, infertility in men and increased chloride concentration in sweat. Although cystic fibrosis is the most common autosomal recessive disease in many Caucasian populations, including those of Europe and the United states with the carrier frequency of about 1:25, it seems that cystic fibrosis prevalence in Iran isn't rare, and in one investigation it has been shown that the carrier frequency is about 1:40 [14]. More than 1800 CFTR mutations and polymorphisms have been identified (CF genetic analysis consortium http://www.genet.sickkids.on.ca/CFTR/).…”

“…Previous molecular studies demonstrated that the Iranian population is very heterogeneous regarding CFTR alleles; as about 50 different mutations were reported in less than a total of 200 CF patients. Many of these alleles were present at a frequency lower than 2% and at least 20% of mutations remained undiagnosed [18,14,20]. As molecular diagnosis is the unique approach to perform prenatal diagnosis in at risk couples, it is though necessary to apply segregation analysis of CFTR polymorphic markers for those families presenting a previous history of the disease with one or two unknown mutations.…”

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

“…High sequence heterogeneity in the CFTR gene of cystic fibrosis patients from this population has also been reported. 40 Ten novel mutations were identified, making a notable contribution to the previously reported mutations. This is important because mutations constitute a tool for understanding the biochemical and physiological role of CYP1B1 in the PCG phenotype.…”

Analysis of the CFTR gene in Iranian cystic fibrosis patients: Identification of eight novel mutations

“…Limited data of CFTR mutations in the Iranian population, in which several ethnic groups are found, are available [18,19]. Therefore we extensively characterized the CFTR gene mutations in 69 well characterized Iranian CF patients.…”