Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in allergic bronchopulmonary aspergillosis
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P W Miller1, A Hamosh, M Macek
1Center for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, USA.
Abstract:
The etiology of allergic bronchopulmonary aspergillosis (ABPA) is not well understood. A clinical phenotype resembling the pulmonary disease seen in cystic fibrosis (CF) patients can occur in some individuals with ABPA. Reports of familial occurrence of ABPA and increased incidence in CF patients suggest a possible genetic basis for the disease. To test this possibility, the entire coding region of the cystic fibrosis transmembrane regulator (CFTR) gene was analyzed in 11 individuals who met strict criteria for the diagnosis of ABPA and had normal sweat electrolytes (< or = 40 mmol/liter). One patient carried two CF mutations (deltaF508/R347H), and five were found to carry one CF mutation (four deltaF508; one R117H). The frequency of the deltaF508 mutation in patients with ABPA was significantly higher than in 53 Caucasian patients with chronic bronchitis (P < .0003) and the general population (P < .003). These results suggest that CFTR plays an etiologic role in a subset of ABPA patients.
Insights
Genetic analysis of cystic fibrosis transmembrane regulator (CFTR) mutations in allergic bronchopulmonary aspergillosis (ABPA) suggests a potential genetic link. CFTR gene mutations were found more frequently in ABPA patients than in controls.
Area of Science:
- Pulmonology
- Genetics
- Immunology
Background:
- The exact causes of allergic bronchopulmonary aspergillosis (ABPA) remain unclear.
- Some ABPA patients exhibit symptoms similar to cystic fibrosis (CF) lung disease.
- Familial cases and higher incidence in CF patients hint at a genetic component in ABPA.
Purpose of the Study:
- To investigate the potential genetic role of the cystic fibrosis transmembrane regulator (CFTR) gene in ABPA etiology.
- To analyze the CFTR gene's coding region in ABPA patients with normal sweat electrolyte levels.
Main Methods:
- Sequencing of the entire coding region of the CFTR gene.
- Analysis of 11 individuals diagnosed with ABPA and normal sweat electrolytes (< or = 40 mmol/liter).
- Comparison of CFTR mutation frequencies in ABPA patients versus controls (chronic bronchitis patients and general population).
Main Results:
- One ABPA patient was a compound heterozygote for two CFTR mutations (deltaF508/R347H).
- Five ABPA patients carried a single CFTR mutation (four deltaF508, one R117H).
- The deltaF508 mutation occurred significantly more often in ABPA patients compared to chronic bronchitis patients and the general population.
Conclusions:
- The findings suggest that the CFTR gene may contribute to the development of ABPA in a subset of patients.
- This implicates CFTR in the pathogenesis of allergic bronchopulmonary aspergillosis.
- Further research into CFTR's role in ABPA is warranted.