Analysis of the CFTR gene in Turkish cystic fibrosis patients: identification of three novel mutations (3172delAC, P1013L and M1028I)

Abstract

In order to determine the spectrum of cystic fibrosis (CF) mutations in the Turkish population, a complete coding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene including exon-intron boundaries, on 122 unrelated CF chromosomes from 73 Turkish CF families was analysed by denaturing gradient gel electrophoresis and multiplex heteroduplex analysis on MDE gel matrix. In addition to 15 previously reported mutations and 12 polymorphisms, three novel mutations, namely 3172delAC, P1013L and M1028I, were detected. DeltaF508 was found to be present on 18.8% of CF chromosomes. The second most common mutation was 1677delTA, with a frequency of 7.3%, followed by G542X and 2183AA-->G mutations, with frequencies of 4.9%. These four most common mutations in Turkish CF population account for approximately 36% of mutations. This study could only detect 52.5% of disease-causing mutations in this population; 47.5% of CF alleles remain to be identified, reflecting the high molecular heterogeneity of the Turkish population.

Cystic fibrosis mutations in Israeli Arab patients

“…The mutation R75X was first described in a German patient (Dork et al 1994) on a different haplotypic background, probably it is a recurrent mutation. The mutation 2183AA>G is common in northern Italy (Bozon et al 1994) and in Turkey (Onay 1998), S549R (A>C) is a rare mutation that was previously described in a single Italian patient (Sangiuolo et al 1991). The del(exon2) mutation was not characterized in detail, a del(exon2) mutation was reported to the "CF consortium Online" (1997) in a Turkish family and it could be the same mutation.…”

A Haplotype Framework for Cystic Fibrosis Mutations in Iran

“…Specifically, the four most common Turkish mutations were found in Iran, including ⌬F508, c.1677delTA, p.G542X, and c.2183AAϾG. 9,29 The p.G542X "Mediterranean mutation," purported to be of Phoenician origin, was found on only one Iranian chromosome, whereas it was relatively frequent (3.6%) among the Turkish CF chromosomes. 6,51 Another common mutations in Iran, p.K1177X, was not found in Turkey but was reported in Bahrain.…”

The Phenotypic Consequences of CFTR Mutations

“…The geographical distribution of CFTR mutations also varies worldwide. Across Europe there is a northwest to southeast gradient in the frequency of F508, with the highest frequency in Denmark (90%), and the lowest frequencies in Turkey, where analysis of 122 unrelated chromosomes from 73 families revealed the prevalence of F508 to be 18.8% (Onay et al 1998), and Romania, where the proportion of CF patients carrying F508 was determined to be 25% (Popa et al 1997). Ashkenazi Jews have a low incidence of F508 but have an increased frequency (60%) of the nonsense mutation W1282X (Shoshani et al 1992).…”