Frequency of CFTR variants in southern Brazil and indication for modulators therapy in patients with cystic fibrosis

Abstract

This is a descriptive cross-sectional study that aims to determine the distribution of the CFTR causing variant in a group of patients at a cystic fibrosis (CF) center in southern Brazil, as well as to describe causing variants that are treatable with mutation-specific drugs. Ninety-two patients from a CF reference center were assessed in this research, all of them with a clinical diagnosis of CF and both alleles identified with pathogenic variants. The most prevalent causing variants were F508del, R1162X, G542X, and N1303K. As for patients with a mutation-specific drug indication, 69.6 % were candidates for the use of Elexacaftor/Tezacaftor/Ivacaftor (Trikafta ® ), 44.6 % for the use of Tezacaftor/Ivacaftor ( Symdeko ® ), and 35.9 % for the use of Lumacaftor/Ivacaftor (Orkambi ® ). For the use of Ivacaftor (Kalydeco ® ), only two patients (2.2 %) were candidates following the Brazilian agency approval. According to the FDA, 10 patients would be candidates for Ivacaftor (10.9 %). Causing variants of classes I and II, which are related to a major severity of the illness, were identified in 135 of 184 alleles (73.3 %). In this study, more than 2/3 of the patients were candidates for the use of CFTR modulators therapy.

Insights Into Cystic Fibrosis Gene Mutation Frequency, Clinical Findings, and Complications Among Pakistani Patients

“…Comparing the distribution of CFTR gene mutations between males and females showed similar patterns, with F508del and N1303K being the most prevalent mutations in both genders. These findings were consistent with previous studies [19,20], indicating that certain CFTR mutations are gender-independent and contribute to CF development in both males and females.…”

Diversity ofCFTRvariants across ancestries characterized using 454,727 UK biobank whole exome sequences

“…As their global distribution and frequencies are poorly understood, we characterized the most common and unique CF-causing variants across populations. Indeed, like previous reports 13,29,30 , F508del was the most common CF-causing variant reported globally. While F508del represented ∼90% of the CF-causing variants found in EUR, our findings indicate its prevalence is much lower in other populations (Fig.…”