title: CFTR gene mutations--including three novel nucleotide substitutions--and haplotype background in patients with asthma, disseminated bronchiectasis and chronic obstructive pulmonary disease.
abstract: In order to investigate the incidence of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and unclassified variants in chronic pulmonary disease in children and adults, we studied 20 patients with asthma, 19 with disseminated bronchiectasis (DB) of unknown aetiology, and 12 patients with chronic obstructive pulmonary disease (COPD), and compared the results to 52 subjects from the general Greek population. Analysis of the whole coding region of the CFTR gene and its flanking intronic regions revealed that the proportion of CFTR mutations was 45% in asthma (P<0.05), 26.3% in DB (P>0.05), 16.7% in COPD (P>0.05), compared to 15.4% in the general population. Seventeen different molecular defects involved in disease predisposition were identified in 16 patients. Three potentially disease-causing mutations, T388 M, M1R and V11I, are novel, found so far only in three asthma patients. The hyperactive M470 allele was found more frequently in COPD patients (frequency 70.8%, P<0.01) than in the controls. The study of the TGmTnM470 V polyvariant CFTR allele revealed the presence of CFTR function-modulating haplotypes TG13/T5/M470, TG11/T5/M470, TG12/T5/V470 and TG12/T7, combined with M470 or V470, in six asthma patients, four DB patients (P<0.01), and two COPD patients (P<0.05). These results confirm the involvement of the CFTR gene in asthma, DB and possibly in COPD.
authors.affiliation: Department of Medical Genetics, Athens University, Aghia Sophia Children's Hospital, Thivon & Livadias, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Tzetis
authors.forename: A
authors.initials: A
authors.lastname: Efthymiadou
authors.forename: S
authors.initials: S
authors.lastname: Strofalis
authors.forename: P
authors.initials: P
authors.lastname: Psychou
authors.forename: A
authors.initials: A
authors.lastname: Dimakou
authors.forename: E
authors.initials: E
authors.lastname: Pouliou
authors.forename: S
authors.initials: S
authors.lastname: Doudounakis
authors.forename: E
authors.initials: E
authors.lastname: Kanavakis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics; D001987:Bronchiectasis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008173:Lung Diseases, Obstructive / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D017354:Point Mutation; D011110:Polymorphism, Genetic
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA