CHEST
Volume 119, Issue 3, March 2001, Pages 762-767
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Clinical Investigations
Frequency of Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations and 5T Allele in Patients With Allergic Bronchopulmonary Aspergillosis

https://doi.org/10.1378/chest.119.3.762Get rights and content

Study objectives:

To assess the frequency of cysticfibrosis transmembrane conductance regulator (CFTR) gene mutations inpatients with allergic bronchopulmonary aspergillosis (ABPA).

Design:

Case-control study. All subjects in the study werescreened for the presence of 13 mutations in the CFTR gene (R117H,621 + 1G->T, R334 W, ΔF508, ΔI507, 1717–1G->A, G542X, R553X, G551D, R1162X, 3849 + 10kbC->T, W1282X, and N1303K). Moreover, theywere also screened for the presence of the 5T variant in intron 8.

Settings:

University hospital and community-basedhospital.

Patients:

Twenty-one white patients with ABPA participated in the study. The presence of CFTR mutations was alsoinvestigated in 43 white subjects with allergic asthma who did not showsensitization to Aspergillus fumigatus and in 142subjects seeking genetic counseling for diseases other than cysticfibrosis (CF).

Results:

Six patients with ABPA werefound to be heterozygous for one CFTR mutation, including ΔF508(n = 2), G542X (n = 1), R1162X (n = 1), 1717–1G->A (n = 1),and R117H (n = 1). The 5T allele was not detected in ABPA patients. None of the ABPA patients showed sweat chloride concentrations > 60mEq/L. The frequency of CFTR mutation carriers was significantly higherin ABPA patients (6 of 21 patients; 28.5%) than in control asthmaticsubjects (2 of 43 subjects; 4.6%; p = 0.01) and in subjects seekinggenetic counseling (6 of 142 subjects; p < 0.001).

Conclusion:

These findings indicate that in patientswith out a clinical diagnosis of CF, CFTR gene mutations could beinvolved in the development of ABPA, in association with other geneticor environmental factors.

Section snippets

Subjects

Subjects included all patients identified as having ABPA (bothwith signs of disease activity and in remission) in the diagnosticregistries of the chest medicine departments of one university hospital(Cliniques Universitaires de Mont-Godinne) and one community-basedhospital (Cliniques St Luc, Bouge), both located in nearbyNamur. The first institution cares for patients from all Wallonia (the French-speaking part of Belgium), while the latter mostly recruits in the Namur province. The diagnosis

Results

Of the 28 patients with a diagnosis of ABPA and who were alive atthe time of the study, 1 patient did not agree to participate in thestudy and 6 patients (2 patients from the community-based hospital)were excluded because they did not meet the above-detailed diagnosticcriteria for ABPA. From the remaining 21 patients, 4 patients came fromthe community-based hospital (patients 5, 16, 17, 18; Table 1). The characteristics of the 21 patients with ABPA are presented inTable 1. Six patients

Discussion

In this study, we found the frequency of the studied CFTRmutations to be significantly higher in ABPA patients than it was ineither allergic asthmatics with out sensitization to Afumigatus or in subjects seeking genetic counseling for reasonsother than CF. These findings are consistent with those reported in astudy by Miller et al,12 although we identified awider spectrum of CFTR mutations in ABPA patients. Theseinvestigators12 analyzed the coding region of the CFTRgene in 11 white patients

ACKNOWLEDGMENT

The authors thank Mss. N. Lanoy and C. Walon fortheir assistance in performing genetic studies, Dr. J. Jamart forperforming statistical analysis, and Mrs. L. Schubert for reviewing thearticle.

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