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DOI: 10.1055/s-2003-39028
Genetics of Idiopathic Disseminated Bronchiectasis
Publication History
Publication Date:
07 May 2003 (online)
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ABSTRACT
Bronchiectasis is an abnormal dilation of bronchi, consequent to the destruction of their walls. It is included in the category of obstructive pulmonary diseases, along with chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis. In approximately 50% of cases, bronchiectasis is associated with underlying conditions; in the remainder, known causes are not ascertainable (idiopathic bronchiectasis). A search for genetic determinants of this phenotype, with the cystic fibrosis gene as a candidate, has been performed by three independent groups. The results of this search agreed on the association of bronchiectasis with cystic fibrosis gene mutations and polymorphisms. The cystic fibrosis gene is also associated with bronchiectasis due to rheumatoid arthritis and allergic bronchopulmonary aspergillosis. A few other genes have been investigated in idiopathic bronchiectasis, with negative results. Idiopathic bronchiectasis is, therefore, to be considered as an obstructive multifactorial disorder belonging to the category of cystic fibrosis monosymptomatic diseases (or CFTR-opathies), whose pathogenesis is influenced by environmental factors and other undetermined genes.
KEYWORDS
Cystic fibrosis - cystic fibrosis gene - environment - multifactorial disorders - obstructive pulmonary disease
REFERENCES
- 1 Luce J M. Bronchiectasis. In: Murray JF, Nadel JA, eds. Textbook of Respiratory Medicine 2nd ed. Philadelphia: WB Saunders 1994: 1398-1417
- 2 Nadel J A. Obstructive diseases. In: Murray JF, Nadel JA, eds. Textbook of Respiratory Medicine 2nd ed. Philadelphia: WB Saunders 1994: 1245-1258
- 3 Pasteur M C, Helliwell S M, Houghton S J. et al . An investigation into causative factors in patients with bronchiectasis. Am J Respir Crit Care Med . 2000; 162 1277-1284
- 4 Luisetti M, Gilè S L, Bombieri C, Benetazzo M G, Pignatti P F. Genetics of chronic obstructive pulmonary disease and disseminated bronchiectasis. Monaldi Arch Chest Dis . 1998; 53 614-616
- 5 Gasparini P, Savoia A, Luisetti M, Peona V, Pignatti P F. The cystic fibrosis gene is not likely to be involved in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol . 1990; 2 297-299
- 6 Kerem B, Rommens J M, Buchanan J A. et al . Identification of the cystic fibrosis gene: genetic analysis. Science . 1989; 245 1073-1080
- 7 Poller W, Faber J-P, Scholz S, Olek K, Müller K-M. Sequence analysis of the cystic fibrosis gene in patients with disseminated bronchiectatic lung disease. Klin Wochenschr . 1991; 69 657-663
- 8 Gervais R, Lafitte J-J, Dumur V. et al . Sweat chloride and ΔF508 mutation in chronic bronchitis or bronchiectasis. Lancet . 1993; 342 997
- 9 Pignatti P F, Bombieri C, Marigo C, Benetazzo M G, Luisetti M. Increased incidence of cystic fibrosis gene mutations in adults with disseminated bronchiectasis. Hum Mol Genet . 1995; 4 635-639
- 10 Pignatti P F, Bombieri C, Benetazzo M G. et al . CFTR gene variant IVS8-5T in disseminated bronchiectasis. Am J Hum Genet . 1996; 58 889-892
- 11 Bombieri C, Benetazzo M G, Saccomani A. et al . Complete mutational screening of the CFTR gene in 120 patients with pulmonary disease. Hum Genet . 1998; 103 718-722
- 12 Girodon E, Cazeneuve C, Labargy F. et al . CFTR gene mutations in adults with disseminated bronchiectasis. Eur J Hum Genet . 1997; 5 149-155
- 13 Tzetis M, Efthymiadou A, Strofalis S. et al . CFTR gene mutations-including three novel nucleotide substitutions-and haplotype background in patients with asthma, disseminated bronchiectasis, and chronic obstructive pulmonary disease. Hum Genet . 2001; 108 216-221
- 14 Cystic Fibrosis Genetic Analysis Consortium Web site: http://www.genet.sickkids.on.ca/cftr Accessed March 2002.
- 15 Chu C-S, Trapnell B C, Curristin S, Cutting G R, Crystal R G. Genetic basis of variable exon 9 skipping in cystic fibrosis transmembrane conductance regulator mRNA. Nat Genet . 1993; 3 151-156
- 16 Highsmith W E, Burch L H, Zhou Z. et al . A novel mutation in the cystic fibrosis gene in patients with pulmonary disease but normal sweat test chloride concentrations. N Engl J Med . 1994; 331 974-980
- 17 Cuppens H, Lin W, Jaspers M. et al . Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes: the polymorphic (TG)m locus explains the partial penetrance of the 5T polymorphism as a disease mutation. J Clin Invest . 1998; 101 487-496
- 18 Benetazzo M G, Gilé L S, Bombieri C. et al . Alpha 1-antitrypsin TAQI polymorphism and α1-antichymotrypsin mutations in patients with obstructive pulmonary disease. Respir Med . 1999; 93 648-654
- 19 Cuvalier A, Muir J-F, Hellot M-F. et al . Distribution of α1-antitrypsin alleles in patients with bronchiectasis. Chest . 2000; 117 415-419
- 20 Patuzzo C, Gilé L S, Zorzetto M. et al . Tumor necrosis factor gene complex in COPD and disseminated bronchiectasis. Chest . 2000; 117 1353-1358
- 21 Puéchal X, Fajac I, Bienvenu T. et al . Increased frequency of cystic fibrosis ΔF508 mutation in bronchiectasis associated with rheumatoid arthritis. Eur Respir J . 1999; 13 1281-1287
- 22 Toussirot E, Despaux J, Wendling D. Increased frequency of HLA-DRB1*0401 in patients with RA and bronchiectasis. Ann Rheum Dis . 2000; 59 1002-1003
- 23 Zielenski J. Genotype and phenotype in cystic fibrosis. Respiration . 2000; 67 117-133
- 24 Weiner Miller P, Hamosh A, Macek Jr M. et al . Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in allergic bronchopulmonary aspergillosis. Am J Hum Genet . 1996; 59 45-51
- 25 Sandford A J, Weir T D, Paré P D. Genetic risk factors for chronic obstructive pulmonary disease. Eur Respir J . 1997; 10 1380-1391
- 26 Barnes P J. Molecular genetics of chronic obstructive pulmonary disease. Thorax . 1999; 54 245-252
- 27 Ferguson G T, Cherniack R M. Management of chronic obstructive pulmonary disease. N Engl J Med . 1993; 328 1017-1022
- 28 O'Brien C, Guest P J, Hill S L, Stockley R A. Physiological and radiological characterisation of patients diagnosed with chronic obstructive pulmonary disease in primary care. Thorax . 2000; 55 635-642
- 29 Wedzicha J A. The heterogeneity of chronic obstructive pulmonary disease. Thorax . 2000; 55 631-632
- 30 Zielenski J, Tsui L C. Cystic fibrosis: genotypic and phenotypic variations. Annu Rev Genet . 1995; 29 777-807
- 31 Dumur V, Gervais R, Rigot J M. et al . Abnormal distribution of the CF delta F508 allele in azoospermic men with congenital aplasia of epididymis and vas deferens [Letter]. Lancet . 1990; 336 512
- 32 Noone P G, Pue C A, Zhou Z. et al . Lung disease associated with the IVS8 5T allele of the CFTR gene. Am J Respir Crit Care Med . 2000; 162 1919-1924
- 33 Boyle M P. Unique presentations and chronic complications in adult cystic fibrosis: do they teach anything about CFTR?. Respir Res . 2000; 1 133-135
- 34 Noone P G, Knowles M R. "CFTR-opathies": disease phenotypes associated with cystic fibrosis transmembrane regulator gene mutations. Respir Res . 2001; 2 328-332
- 35 Chillon M, Casals T, Mercier B. et al . Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med . 1995; 332 1475-1480
- 36 Zielenski J, Patrizio P, Corey M. et al . CFTR gene variant for patients with congenital absence of vas deferens. Am J Hum Genet . 1995; 57 958-960