The Impact of the Complexity of Cystic Fibrosis in Jordanian Patients on the Spectrum of Cystic Fibrosis Transmembrane Conductance Regulator Mutations

摘要

Contrary to earlier beliefs, cystic fibrosis (CF) is relatively common in Arab populations with an estimated incidence of about 1/2500 live births in Jordan. In order to identify the common mutations among CF Jordanian patients a total of 386 Jordanian CF patients (323 families) were followed up over a period of fifteen years from diagnosis and were screened for Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutations. Furthermore, to characterize the spectrum of the CFTR mutations, DNA samples were obtained from sixty-eight patients and sixty-six parents and were subjected to complete CFTR gene screening by multiplex heteroduplex (mHET) analysis followed by direct sequencing. The screening included promoter, all exons with flanking intron sequence (including T-tract in intron 8) and resulted in the identification of twenty-six different mutations. The most prevalent mutation, p.Phe508del was found to account only for 7.4 % of the identified CFTR mutations. This low frequency of the p.Phe508del mutation among Jordanian patients is comparable with native Asians. In this study, seven CFTR mutations, which have not been previously reported, were identified (c.CFTR dele2 (ins186), c.296+9AT, c.297-10TG, p.Thr388Met, p.Thr760Met, c.3670delA and c.4006delA). The large number of mutations reflects the ethnic diversity of the Jordanian population and the complex history of the country. The obtained results will assist to improve the understanding of the molecular basis of the pathophysiology of cystic fibrosis, genetic counseling, and prenatal diagnosis in Jordan. Additionally, it will identify the correlation between the CFTR genotypes and the CF phenotypes in the Jordanian population, especially among the newly discovered mutations, which will, in turn, broaden the management of the disease in Jordan.