Epidemiological Evaluation of Next-Generation Sequencing and MLPA Results in Patients with a Presumptive Cystic Fibrosis Diagnosis

Abstract

Cystic fibrosis is an autosomal recessive disease caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The spectrum and frequencies of CFTR mutations vary among populations. As a result of continuous migration around the world, the frequency of CF variants may change and is still unclear in some geographies. We aimed to define the CFTR gene variants we observed as a result of our single-center experience. This research assessed the outcomes of 353 patients who underwent next-generation sequencing to identify variations in the CFTR gene. Variants classified as clinically uncertain significance, likely pathogenic or pathogenic detected in patients with pre-diagnosis of cystic fibrosis who underwent genetic testing were included in the evaluation. The variants detected in the vast majority of cases were comparable to those found in other populations. However, some variants showed significant differences in allele frequencies when compared to European and Asian populations. Mutations were detected in 25.2% of cases. This dataset revealed that the most common mutations in patients presenting to our center were c.2991G>C, c.2856G>C, c.1545_1546delTA, c.1521_1523 del and c.202A>G. This research presents data on CFTR variations to determine the frequency of CF in the Istanbul province of our nation and to identify additional frequently occurring pathogenic variants that are currently unknown. This kind of research has the potential to facilitate the creation of a localized strategy for maximizing healthcare provision for individuals with CF.