Cystic fibrosis in Lebanon: distribution of CFTR mutations among Arab communities

Abstract

Cystic fibrosis (CF) is thought to be rare among the Arab populations from the Middle East and little data have been reported so far. We have studied a sample of 20 families living in Lebanon for several generations and who have at least one child with CF. These families are mainly from the Maronite, Greek Catholic, Greek Orthodox. Shiite or Sunnite groups. We found a 50% rate of consanguineous marriage, independent of the community of origin. The distribution of CF genotypes was determined through the screening of all exons of the CFTR (cystic fibrosis transmembrane conductance regulator) gene by the technique of denaturing gradient gel electrophoresis combined with asymmetric amplification DNA sequencing. A total of ten different mutations accounting for 87.5% of 32 unrelated CF alleles was identified, including two novel putative mutations (E672del and IVS21-28G-->A). Three mutations, delta F508 (37.5%), W1282X (15.6%), and N1303K (9.4%) accounted for 62.5% of CF alleles. Interestingly, in the Maronite group, 66.7% of the delta F508 chromosomes were found to be associated with allele 7 of the IVS8(T)tract, contrasting with the absolute linkage disequilibrium between European delta F508 chromosomes and allele 9. During this study, two previously undescribed polymorphisms (IVS14a + 17del5 and 2691T/C) were also identified.

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

“…This could be due to different spectrum of mutations in those populations and a high prevalence of p.Phe508del which is tightly linked to T 9 allele in Caucasians [17,29]. However in one study performed in the Maronite group in Lebanon, 66.7% of the p.Phe508del chromosomes were found to be associated with T 7 allele [31] suggesting a different origin of p.Phe508del in this later population. In the few studies performed in Iranian CF patients, various mutations were reported in CFTR gene.…”

“…As the diagnosis of CF was certain according to Rosenstein and Farrell [11,12], for those 4 CF patients presenting T5 allele, there should be a CFTR mutation in cis with T5 as CFTR related diseases did not apply to these patients. All studies on polyT polymorphism showed a predominance of T 7 allele in normal individuals [17,[24][25][26][27][28][29][30][31] but Caucasians and Indians CF patients seemed to have different frequency of T 7 allele. This could be due to different spectrum of mutations in those populations and a high prevalence of p.Phe508del which is tightly linked to T 9 allele in Caucasians [17,29].…”

“…In Caucasians the T 9 is predominant, while in Indians the T 7 allele is predominant [17,29]. This difference could be explained by different spectrum and frequency of mutations among those populations but the haplotype studies of p.Phe508del and polyT polymorphism appeared again to be controversial among different populations [17,29,31]. Thus further population studies seems necessary to elucidate the multi-origin of p.Phe508del.…”

Cystic fibrosis mutations in Israeli Arab patients

“…There are only a few studies of CF mutations in patients from the Middle East, including a study of Saudi Arabian patients (el-Harith et al 1997), of Lebanese patients (DesGeorges et al 1997) and of Turkish patients (Onay et al 1998). The common CF mutations in the Israeli Arabs and the Lebanese patients were ∆F508, N1303K, W1282X and 4010delTATT, the Turkish CF patients were ∆F508, N1303K, W1282X, G542X and 2183AA>G and the Saudi Arabian patients N1303K.…”

Cystic Fibrosis testing among Arab-Americans

“…Although we are unaware of any published data regarding CF population carrier screening among Arab-Americans, several studies have reported the mutation distribution among Arabic CF patients. 12,13,14 Combining these studies, a total of 96 CF patients from 93 different Arabic families were analyzed. Among the 93 different families, 26 different mutations were identified with the results summarized in Table 3.…”