Abstract
A detailed comparison of the severity of chest disease with mutational status was carried out by cross sectional study of 127 cystic fibrosis patients, aged 1 to 31 years, living in Wales. Lung disease was classified according to severity, depending on pulmonary function tests (carried out on 76 patients) and chest radiograph status; information was obtained also on age at diagnosis in relation to severity of chest disease and colonisation with Pseudomonas species. Genotypes were determined by analysis for the mutations delta F508, delta I507, G551D, R553X, G542X, R117H, R560T, 1717--IG > A, and 621 + 1G > T. CF patients homozygous positive and heterozygous for the delta F508 deletion showed a significant decline of lung function with age. Unlike other studies, we did not find patients homozygous positive for the delta F508 deletion to have poorer lung function compared with heterozygous patients. Patients with the genotype 621 + IG > T/delta F508 tended to have more severe chest disease than the delta F508 homozygous patients in the same age group. There was some evidence that four patients heterozygous for R117H have mild chest disease.
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- Boschetto P., Rogers D. F., Fabbri L. M., Barnes P. J. Corticosteroid inhibition of airway microvascular leakage. Am Rev Respir Dis. 1991 Mar;143(3):605–609. doi: 10.1164/ajrccm/143.3.605. [DOI] [PubMed] [Google Scholar]
- Chrispin A. R., Norman A. P. The systematic evaluation of the chest radiograph in cystic fibrosis. Pediatr Radiol. 1974;2(2):101–105. doi: 10.1007/BF01314939. [DOI] [PubMed] [Google Scholar]
- Dean M., White M. B., Amos J., Gerrard B., Stewart C., Khaw K. T., Leppert M. Multiple mutations in highly conserved residues are found in mildly affected cystic fibrosis patients. Cell. 1990 Jun 1;61(5):863–870. doi: 10.1016/0092-8674(90)90196-l. [DOI] [PubMed] [Google Scholar]
- Johansen H. K., Nir M., Høiby N., Koch C., Schwartz M. Severity of cystic fibrosis in patients homozygous and heterozygous for delta F508 mutation. Lancet. 1991 Mar 16;337(8742):631–634. doi: 10.1016/0140-6736(91)92449-c. [DOI] [PubMed] [Google Scholar]
- Kerem B., Rommens J. M., Buchanan J. A., Markiewicz D., Cox T. K., Chakravarti A., Buchwald M., Tsui L. C. Identification of the cystic fibrosis gene: genetic analysis. Science. 1989 Sep 8;245(4922):1073–1080. doi: 10.1126/science.2570460. [DOI] [PubMed] [Google Scholar]
- Kerem E., Corey M., Kerem B. S., Rommens J., Markiewicz D., Levison H., Tsui L. C., Durie P. The relation between genotype and phenotype in cystic fibrosis--analysis of the most common mutation (delta F508). N Engl J Med. 1990 Nov 29;323(22):1517–1522. doi: 10.1056/NEJM199011293232203. [DOI] [PubMed] [Google Scholar]
- Riordan J. R., Rommens J. M., Kerem B., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J. L. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066–1073. doi: 10.1126/science.2475911. [DOI] [PubMed] [Google Scholar]
- Rommens J. M., Iannuzzi M. C., Kerem B., Drumm M. L., Melmer G., Dean M., Rozmahel R., Cole J. L., Kennedy D., Hidaka N. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059–1065. doi: 10.1126/science.2772657. [DOI] [PubMed] [Google Scholar]
- Santis G., Osborne L., Knight R. A., Hodson M. E. Independent genetic determinants of pancreatic and pulmonary status in cystic fibrosis. Lancet. 1990 Nov 3;336(8723):1081–1084. doi: 10.1016/0140-6736(90)92566-z. [DOI] [PubMed] [Google Scholar]
- Santis G., Osborne L., Knight R. A., Hodson M. E. Linked marker haplotypes and the delta F508 mutation in adults with mild pulmonary disease and cystic fibrosis. Lancet. 1990 Jun 16;335(8703):1426–1429. doi: 10.1016/0140-6736(90)91448-j. [DOI] [PubMed] [Google Scholar]