Cystic fibrosis: The ΔF508 mutation does not lead to an exceptionally severe phenotype. A cohort study

Abstract

In an attempt to ascertain a relationship between genotype and phenotype, we studied the pulmonary and nutritional status of 123 cystic fibrosis patients with known genotype at an age of 8.5-10 years. Patients represent a cohort as they are almost all those born and diagnosed in a given area and period. They were followed at a single centre using uniform diagnostic and treatment protocols. Pulmonary and nutritional status of homozygous delta 508 patients did not differ from that of compound heterozygotes or of patients with other unspecified genotypes. Pulmonary manifestations varied widely in all genotype groups. With the given number of patients, a slightly higher mortality of delta F508 homozygotes could have been coincidental. We conclude that up to the age of 8.5-10 years the severity of pulmonary lesions and nutritional deficiencies is not related to the delta F508 mutation.

Correlation between nasal potential difference measurements, genotype and clinical condition in patients with cystic fibrosis

“…Homozygotes for ∆F508 mutation have been found to have a greater incidence of pancreatic insufficiency, worse lung function and higher mortality compared to other genotypes [2,3] while isolated mutations such as A455E are associated with a mild clinical course [4]. However, a cohort study in Italy showed that pulmonary status in 8.5-10 yr old ∆F508 homozyotes was no different from that in other mutations [5]. Indeed, the conclusion from a large phenotype genotype consortium [6] was that the only prognostic value of genotypic information is for the prediction of pancreatic sufficiency.…”

Identification of Unique Pattern of CFTR Gene Mutations in Cystic Fibrosis in an Ethnic Kashmiri Population (North India)

“…Studies focusing on pulmonary status as a function of the Δ508del allele have reported a wide range of effects, from a detectable impact of CFTR genotype to no or statistically insignificant influences [34,35]. Other studies using more refined assessment of CFTR mutations have shown statistically significant correlations between CFTR genotypes and pulmonary status, whereas still others have failed to detect a significant association [36].…”

Genotype-phenotype relationships in a cohort of adult cystic fibrosis patients

“…KEREM et al [5] showed that ∆F508 homozygotes almost always have pancreatic insufficiency, whereas 28% of ∆F508 compound heterozygotes and 64% of patients who do not carry a ∆F508 mutation have adequate pancreatic function. In contrast, no correlation was found between the ∆F508 genotype and pulmonary status [5][6][7][8][9][10][11]. In the majority of studies [5,6,8,9,11], the lack of correlation between genotype and pulmonary status might, in part, be explained by selection of young patients (mean age ranging 9-18 yrs), which may give insufficient background to assess the long-term outcome of pulmonary involvement.…”

“…In contrast, no correlation was found between the ∆F508 genotype and pulmonary status [5][6][7][8][9][10][11]. In the majority of studies [5,6,8,9,11], the lack of correlation between genotype and pulmonary status might, in part, be explained by selection of young patients (mean age ranging 9-18 yrs), which may give insufficient background to assess the long-term outcome of pulmonary involvement. In two studies which focused on CF adult patients only [7,10], and in most other studies [5,6,8,9], comparison between homozygotes or compound heterozygotes for the ∆F508 mutation were made without differentiating compound heterozygotes according to the type of their non-∆F508 mutation, which may influence the severity of the pulmonary outcome.…”

“…In the majority of studies [5,6,8,9,11], the lack of correlation between genotype and pulmonary status might, in part, be explained by selection of young patients (mean age ranging 9-18 yrs), which may give insufficient background to assess the long-term outcome of pulmonary involvement. In two studies which focused on CF adult patients only [7,10], and in most other studies [5,6,8,9], comparison between homozygotes or compound heterozygotes for the ∆F508 mutation were made without differentiating compound heterozygotes according to the type of their non-∆F508 mutation, which may influence the severity of the pulmonary outcome. KUBESCH et al [12], who classified ∆F508 compound heterozygotes according to the type of non-∆F508 mutation, showed genetic determinants for the colonization of airways by Pseudomonas aeruginosa, but not for pulmonary function.…”