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

CFTR modulators have significantly affected the prognosis for cystic fibrosis, improving the clinical course in most patients with the F508del variant and several other <i>CFTR</i> 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 <i>in vitro</i>. 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.