Abstract
In an attenmpt to ascertain a relationship between genotype and phenotype, we studied the pulmonary and nutritional status of 123 cystic fibrosis patients with known genotype at an age of 8.5–10 years. Patients represent a cohort as they are almost all those born and diagnosed in a given area and period. They were followed at a single centre using uniform diagnostic and treatment protocols. Pulmonary and nutritional status of homozygous ΔF508 patients did not differ from that of compound heterozygotes or of patients with other unspecified genotypes. Pulmonary manifestations varied widely in all genotype groups. With the given number of patients, a slightly higher mortality of ΔF508 homozygotes could have been coincidental. We conclude that up to the age of 8.5–10 years the severity of pulmonary lesions and nutritional deficiencies is not related to the ‡F508 mutation.
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Abbreviations
- CF:
-
cystic fibrosis
- FEV1 :
-
forced expiratory volume in is
- FVC:
-
forced vital capacity
- PI:
-
pancreas insufficient
- PS:
-
pancreas sufficient
References
Barlocco EG, Benettazzo D, Borgo G et al (1987) Historical course of neonatal screening for cystic fibrosis in Veneto and surrounding areas. Evaluation over 12.8 years. In: Kuzemko JA, Joint GS (eds) Insights into pediatrics Gardner-Caldwell, Macclesfield, pp 1:5–12
Borgo G, Mastella G, Gasparini P, Zorzanello A, Doro R, Pignatti PF (1990) Panereatic function and gene deletion ‡F508 in cystic fibrosis. J Med Genet 27:665–669
Borgo G, Mastella G, Gasparini P, Pignatti PF (1990) Genetic analysis and pancreatic function in cystic fibrosis. Lancet I:1601
Britton JR (1989) Effects of social class, sex and region of residence on age of death for cystic fibrosis. BMJ 298:483–487
Campbell P, Philips J, Krishnamani S, et al (1991) Cystic fibrosis: relationship between clinical status and ‡F508 deletion. J Pediatr 118:239–241
Chrispin AR, Norman AP (1974) The systematic evaluation of the chest radiograph in CF. Pediatr Radiol 2:101–110
Collins FS (1991) The gene two years later: progress and projections. Pediatr Pulmonol [Suppl] 6:61–65
Curtis A, Nelson R, Porteous M (1991) Association of less common cystic fibrosis mutations with a mild phenotype. J Med Genet 28:34–37
Danker-Roelse JE, Meerman GJ, Martijn A (1989) Survival and clinical outcome in patients with cystic fibrosis, with or without neonatal screening. J Pediatr 114:362–367
Estivill X, Chillon M, Casals T et al (1989) ‡F508 gene deletion in cystic fibrosis in Southern Europe. Lancet II:1404
Figarella C, Taulier G, Sarles H (1965) Dosage de la chymotrypsine et de la trypsine dans le suc duodénal. Bull Soc Chim Biol 47:679–684
Gaskin KJ (1988) The impact of nutrition in cystic fibrosis: a review. J Pediatr Gastroenterol Nutr 7 [Suppl 1]:12–17
Gasparini P, Borgo G, Mastella G, Bonizzato A, Dognini M, Pignatti PF (1992) Nine cystic fibrosis patients homozygous for CFTR nonsense mutation R1162X have mild or moderate lung disease. J Med Genet 29:558–562
Hibbert ME, Lannigan A, Landav LI (1989) Lung function values from a longitudinal study of healthy children and adolescents. Pediatr Pulmonol 7:101–109
Hudson I, Phelan PD (1987) Are sex, age at diagnosis or mode of presentation prognostic factors for cystic fibrosis? Pediatr Pulmonol 3:288–297
Jeejeebhoy KN, Ahmed S, Kozek G, et al (1970) Determinations of fecal fats containing both medium and long chain triglycerides and fatty acids. Clin Biochem 3:157–161
Johansen H, Nit M, Hoiby N, et al (1991) Severity of cystic fibrosis in patients homozygous and heterozygous for ΔF508. Lancet 337:631–634
Kerem BS, Rommens JM, Buchanan A et al (1989) Identification of the cystic fibrosis gene: genetic analysis. Science 245:1073–1080
Kerem E, Corey M, Kerem BS, et al (1990) The relation between genotype and phenotype in cystic fibrosis⊕nalysis of the most common mutation (‡F508). N Engl J Med 323: 1517–1522
Kerem E, Reisman J, Corey M et al (1992) Prediction of mortality in patients with cystic fibrosis. N Engl J Med 326:1187–1191
Kristidis P, Bozon D, Corey M, et al (1992) Genetic determination of exocrine pancreatic function in cystic fibrosis. Am J Hum Genet 50:1178–1184
Mastella G, Barbato G, Trabucchi C et al (1975) The exocrine pancreas in cystic fibrosis. Ital J Pediatr 1:109–130
Nunes V, Gasparini P, Novelli G et al (1991) Analysis of 14 cystic fibrosis mutations in five South European populations Hum Genet 87:737–738
Osborne L, Knight D, Santis G, et al (1991) No alternative splicing or stop mutations in homozygous ΔF508 patients with very mild pulmonary disease. Pediatr Pulmonol [Suppl 6] 97:249
Padoan R, Bettinelli ME, Cesana B et al. (1991) Survival in cystic fibrosis. Prognostic factors in the Italian population. Ital J Pediatr 17:669–679
Pederzini F, Faraguna D, Giglio L, et al (1990) Development of a screening system for cystic fibrosis: meconium or blood spot trypsin assay or both? Acta Pediatr Scand 79:935–942
Pignatti PF (1991) Cystic fibrosis gene mutations, and correlations with clinical manifestations. Pathol Biol 39:582–584
Riordan JR, Rommens JM, Kerem BS, et al (1989) Identification of the cystic fibrosis gene: cloning and characterisation of complementary DNA. Science 245:1066–1072
Rommens JM, Iannuzzi MC, Kerem BS, et al (1989) Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245:1059–1065
Rommens JM, Kerem BS, Greer W, et al (1990) Rapid nonradioactive detection of the major cystic fibrosis mutation Am J Hum Gen 46:395–396
Sampé M, Pedron G, Roy-Pernot MP (1979) Auxologie: méthode et séquences. Laboratoires Therapix, Paris
Santis G, Osborne L, Knight R, et al (1990) Independent genetic determinants of pancreatic and pulmonary status in cystic fibrosis. Lancet 336:1081–1084
Stuhrmann M, Macec M, Reis A, et al (1990) Genotype analysis of cystic fibrosis patients in relation to pancreatic sufficiency. Lancet I:738–739
Warwick WJ (1982) Prognosis for survival with CF: the effects of early diagnosis and CF Center care. Acta Pediatr Scand [Suppl] 301:27
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Borgo, G., Gasparini, P., Bonizzato, A. et al. Cystic fibrosis: The ΔF508 mutation does not lead to an exceptionally severe phenotype. A cohort study. Eur J Pediatr 152, 1006–1011 (1993). https://doi.org/10.1007/BF01957227
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DOI: https://doi.org/10.1007/BF01957227