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.
Highlights
Cystic fibrosis (CF) is an autosomal recessive genetic disease, which is characterized by causing variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, that is located in chromosome 7
Values between 30 and 59 mmol/l are considered borderline. Another way to carry out confirmation is through the search for pathogenic variants, through panels, or sequencing of the CFTR gene, with the identification of mutations in two alleles (Athanazio et al, 2017)
Variants of CFTR are categorized into six classes of causing variants, according to their functional effects: Class I results in no protein production; class II causes the retention of an unfolded protein in the endoplasmic reticulum, which results in the absence or diminished protein function; class III affects the regulation of the channel; class IV affects conductance; class V causes a significant reduction of mRNA or protein; class VI causes protein instability in the plasma membrane
Summary
Cystic fibrosis (CF) is an autosomal recessive genetic disease, which is characterized by causing variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, that is located in chromosome 7. With the development of new therapies, which have specific genetic causing variants as targets, the knowledge of the local CFTR variation frequency is essential to improve patient care and for treatment cost estimative. Ivacaftor is indicated for patients that have one of the 38 CFTR causing variants responsive to the in vitro test or to the clinical test.
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