RESUMEN
BACKGROUNDS: Genetic variants in CF transmembrane conductance regulator (CFTR) gene causes cystic fibrosis (CF), a prevalent autosomal recessive disorder. More than 2000 variants in CFTR have been described as disease causative. This study aims to delineate the genotypic and phenotypic landscape of CF among people with CF (pwCF) followed at the largest CF center in Turkey. METHODS: We conducted a descriptive and retrospective analysis of 481 patients registered with the European CF Society Patient Registry and followed at Marmara University Selim Çöremen CF Center from 2015 onwards. Comprehensive CFTR analysis was utilized for genetic diagnosis. Besides the whole cohort, novel variants and complex alleles were also described. RESULTS: Our cohort exhibited a broad spectrum of CFTR variants, with 136 different variants detected, indicating substantial genetic diversity. The F508del variant was less prevalent in our cohort compared to US and European averages, which could reflect unique genetic and demographic characteristics of the Turkish population. Additionally, we identified nine novel variants in 12 alleles, which enhances the understanding of CF's genetic complexity in this region, and complex alleles in 32 pwCF. CONCLUSION: Our research underscores the heterogeneity of CFTR variants in Turkey and highlights the necessity for extensive genetic profiling particularly for diverse populations to provide effective personalized treatment strategies. It is crucial to understand the full spectrum of CFTR variants with the advent of CFTR modulators.
RESUMEN
BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease caused by variants of CFTR gene. Over 2000 variants have been identified, and new drugs called CFTR modulators have been developed to target specific defects in the CFTR protein. However, these drugs are only suitable for patients with certain variants of CFTR, and eligibility rates vary depending on race and geographical region. This study aimed to reveal the detailed genotype and clinical characteristics of people with CF (pwCF) at our center in Turkey, a developing country, who are not eligible for CFTR modulators. METHODS: A total of 445 pwCF followed up at Marmara University were reviewed retrospectively. Variants of the patients ineligible to CFTR modulators were classified based on American College of Medical Genetics guidelines, CFTR classification, the change in the encoded protein, and the variant type. RESULTS: The study revealed that 139 (31.2%) patients weren't eligible for CFTR modulators. There were 60 different variants in the 276 alleles, as two were missing. The majority of patients had missense or nonsense variants, and that the most common variant was c.1545_1546del, which can be said unique to this geography. CONCLUSION: The study highlights the importance of detecting the variants of ineligible patients in detail to guide future approaches for more targeted and effective interventions in CF care. Testing the effectiveness of CFTR modulators for rare or newly occurring variants is crucial to ensure equal access for pwCF to these therapies from different racial backgrounds and ethnic minorities.