Mutations of the CFTR gene and novel variants in Turkish patients with cystic fibrosis: 24-years experience

• Published in: Clinica chimica acta 2020-11, Vol.510, p.252-259
• Main Authors: Dayangaç-Erden, Didem, Atalay, Merve, Emiralioğlu, Nagehan, Hızal, Mina, Polat, Sanem, Özçelik, Uğur, Yalçın, Ebru, Doğru, Deniz, Yılmaz, Engin, Kiper, Nural
• Format: Article
• Language: English
• Subjects: Cystic fibrosis; Cystic Fibrosis - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Exons; Genetic screening; Genotype- phenotype correlation; Humans; In silico analysis; Mutation; Novel variants; Personalized medicine; Turkey
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2020.07.033

•Mutations among Turkish cystic fibrosis patients show heterogeneity.•It is difficult to establish genotype phenotype correlations.•By sequencing it is possible to increase the mutation detection rate to 76.7%.•For personalized treatments it is necessary to characterize novel variants.•Insilico tools predict novel variants prior to RNA and protein based approaches. Cystic fibrosis, the most prevalent autosomal recessive genetic disease, is caused by mutations in the CFTR gene. The spectrum and frequency of CFTR mutations in Turkish patients show heterogeneity. We investigated CFTR gene mutations in samples from 604 cystic fibrosis patients diagnosed at Hacettepe University, the largest referral CF center in Turkey, by different techniques such as strip assay and direct sequencing. We also analyzed the effects of novel variants and predicted pathogenicity by integrating information from different insilico tools. We showed that mutation detection rate increased to 76.7% with direct sequencing of the coding region and exon/intron boundaries. Ten variants were described for the first time. All variants except T788R were reported as pathogenic. Characterization of patients with CFTR mutations that occur at very low frequencies is necessary for mutation-based treatments. Population specific genetic screening panels should be designed since none of them are suitable for Turkish patients due to heterogeneous mutation distribution. The preliminary data obtained from in silico results of novel variants will pave the way for functional analysis by using samples obtained from patients. These observations will facilitate the discovery and development of new targeted and personalized therapies.