Study of the impact of the complex allele [L467F;F508del] on the clinical phenotype of cystic fibrosis: comparing patients with [L467F;F508del]/class I and F508del/class I genotypes

Cystic fibrosis (CF) is an autosomal recessive disease caused by CFTR mutations. The presence of complex alleles can modify the clinical phenotype, but data on the impact of [L467F;F508del] are limited.

The aim of the study was to compare the clinical manifestations in two cohorts of Russian patients with cystic fibrosis (CF) under 18 years of age with [L467F;F508del]/class I or F508del/class I genotype of CFTR.

Methods. A single-center retrospective cohort study was conducted using data from the Russian National CF Patient Registry for 2023. The study included 100 patients under 18 years: 22 with the [L467F;F508del]/class I genotype (group 1) and 78 with F508del/class I (group 2). The study compared their age at enrollment, sex, age at diagnosis, proportion of diagnoses established through neonatal screening, history of meconium ileus, airway microbiological profile, lung function, nutritional status, frequency of complications, and ongoing therapy.

Results. The groups were comparable in terms of age, sex, age at diagnosis, and neonatal screening results. No statistically significant differences were observed in lung function or nutritional status. The frequency of liver cirrhosis was higher in the [L467F;F508del]/class I group (22.7% vs 5.1%; p = 0.038). This group also had a higher prevalence of Achromobacter spp. colonization (13.6% vs 2.6%; p = 0.044). No significant differences were found for other complications.

Conclusion. The presence of the [L467F;F508del] complex allele does not lead to statistically significant changes in lung function or nutritional status compared to F508del/class I, but may influence the microbiological profile and the frequency of liver involvement. These findings highlight the importance of molecular-genetic characterization of complex CFTR alleles for risk stratification and the planning of personalized therapy in children with cystic fibrosis.

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