A Haplotype Framework for Cystic Fibrosis Mutations in Iran Publisher Pubmed



Elahi E^{1, 2, 3} ; Khodadad A⁴ ; Kupershmidt I⁵ ; Ghasemi F^{1, 2} ; Alinasab B³ ; Naghizadeh R¹ ; Eason RG³ ; Amini M⁶ ; Esmaili M⁷ ; Esmaeili Dooki MR⁸ ; Sanati MH² ; Davis RW³ ; Ronaghi M³ ; Thorstenson YR³ Show Affiliations
Source: Journal of Molecular Diagnostics Published:2006

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 disease-causing 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, under-diagnosed 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, ΔF508 (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. Copyright © American Society for Investigative Pathology and the Association for Molecular Pathology.