title: Next generation sequencing to determine the cystic fibrosis mutation spectrum in Palestinian population.
abstract: An extensive molecular analysis of the CF transmembrane regulator (CFTR) gene was performed to establish the CFTR mutation spectrum and frequencies in the Palestinian population, which can be considered as an understudied population. We used a targeted Next Generation Sequencing approach to sequence the entire coding region and the adjacent sequences of the CFTR gene combined with MLPA analysis of 60 unrelated CF patients. Eighteen different CF-causing mutations, including one previously undescribed mutation p.(Gly1265Arg), were identified. The overall detection rate is up to 67%, and when we consider only CF patients with sweat chloride concentrations >70 mEq/L, we even have a pickup rate of 92%. Whereas p.(Phe508del) is the most frequent allele (35% of the positive cases), 3 other mutations c.2988+1Kbdel8.6Kb, c.1393-1G>A, and p.(Gly85Glu) showed frequencies higher than 5% and a total of 9 mutations account for 84% of the mutations. This limited spectrum of CF mutations is in agreement with the homozygous ethnic origin of the Palestinian population. The relative large portion of patients without a mutation is most likely due to clinical misdiagnosis. Our results will be important in the development of an adequate molecular diagnostic test for CF in Palestine.
authors: Department Master Program in Clinical Laboratory Science, Birzeit University, 9700 Birzeit, State of Palestine.
authors: O
authors: O
authors: Essawi
authors: Department Master Program in Clinical Laboratory Science, Birzeit University, 9700 Birzeit, State of Palestine.
authors: M
authors: M
authors: Farraj
authors: Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium.
authors: K
authors: K
authors: De Leeneer
authors: Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium.
authors: W
authors: W
authors: Steyaert
authors: Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium.
authors: K
authors: K
authors: De Pauw
authors: Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium.
authors: A
authors: A
authors: De Paepe
authors: Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium.
authors: K
authors: K
authors: Claes
authors: Department Master Program in Clinical Laboratory Science, Birzeit University, 9700 Birzeit, State of Palestine.
authors: T
authors: T
authors: Essawi
authors: Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium.
authors: P J
authors: PJ
authors: Coucke
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002712:Chlorides / Q000032:analysis; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007223:Infant; D008297:Male; D008877:Middle East; D009154:Mutation; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*; D013542:Sweat / Q000737:chemistry
chemical_list: D002712:Chlorides