Work

L467F;F508del Complex Allele in a Heterozygous State with CFTRdele2,3: What to Expect from CFTR Modulators?

Year: 2025

Type: article

Abstract: CFTR modulators have significantly affected the prognosis for cystic fibrosis, improving the clinical course in most patients with the F508del variant and several other CFTR gene variants. The presence of complex alleles, including more than one variant in the cis position, can change the properties of the protein and the efficacy of modulators. Objective: We aimed to describe the efficacy of CFTR modulators in the treatment of two siblings with the c.[1521_1523delCTT;1399C>T];[54-5940_273+10250del21kb] (L467F;F508del/CFTRdele2,3) genotype in clinical practice and in vitro. This article presents the clinical presentation and results of CFTR channel function assessment and personalized selection of CFTR modulators in monochorionic diamniotic twins with cystic fibrosis and the L467F;F508del/CFTRdele2,3 genotype. This is the first demonstration of the efficacy of a new CFTR modulator in patients with a complex allele and a class I variant in the genotype. The obtained results may be useful for choosing treatment strategies for patients with a complex allele and a class I variant in the genotype.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms262311742