CFTR GENE-MUTATIONS IN ADULTS WITH DISSEMINATED BRONCHIECTASIS

The severity and type of clinical manifestations are variable in patie nts with cystic fibrosis (CF). The respiratory syndromes in these pati ents consist of lung infections associated with disseminated bronchiec tasis (DB), asthma, and chronic obstructive pulmonary disease. To inve stigate the possible involvement of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in chronic pulmonary disease in adul ts, we studied 32 DB patients with a clinically isolated respiratory s yndrome. Careful analysis of all the CFTR gene exons and their flankin g regions revealed a significantly increased frequency of CFTR gene mu tations in these patients. Thirteen CFTR gene mutations were identifie d in sixteen different alleles. Six of these mutations, which have pre viously been reported as CF defects, were found on nine alleles. A fur ther four, two of which had not previously been described (D192N and 4 06-2 A Delta C), are potentially disease-causing mutations. We also id entified three rare substitutions (R31C, L997F, T1220I), which could b e involved in mild CFTR gene disease. Four patients were compound hete rozygotes, one carried two CFTR gene mutations (possibly allelic) and six were heterozygous for a mutation. These results indicate that CFTR gene mutations may play a role in bronchiectatic lung disease, possib ly in a multifactorial context. These findings have implications for g enetic counselling of DB patients and their families.