Screening by high-throughput sequencing for pathogenic variants in cystic fibrosis: Benefit of introducing personalized therapies

Abstract

This short report documented cystic fibrosis transmembrane conductance regulator (CFTR) variants in 37 patients with cystic fibrosis (CF) in the Rio Grande do Norte region of Northeast Brazil. The high-throughput sequencing technology (HTS) genetic testing provided a definitive molecular diagnosis in 31 patients (83.8%). Among them, 25 patients' carriers of the c.1521_1523delCTT variant, categorized as a class 2 mutation, can be currently treated with CFTR modulator drugs. Five children aged 2-5 years could benefit from double lumacaftor/ivacaftor therapy, and 20 patients aged >6 years could be treated with the triple-combination elexacaftor/tezacaftor/ivacaftor therapy. Thus, the identification of pathogenic variants associated with the development of this disease allows for the introduction of therapy with CFTR modulators that favour better patient management.

Keywords: CFTR gene; CFTR modulators therapies; cystic fibrosis; high-throughput sequencing; variants.