Cystic fibrosis (CF) is a lethal autosomal recessive disorder characterized by obstructive pulmonary disease, pancreatic exocrine deficiency, high content of sodium and chloride in the sweat, and male infertility (Table 1). The CF phenotype is highly variable among unrelated individuals and within families, although certain manifestations, such as pancreatic status, are similar among affected siblings. At least three factors contribute to variability of the CF phenotype: mutations in the CF gene, genetic background, and environment.<sup>26 Cutting G.R. Cystic Fibrosis Emery and Rimoin's Principals and Practice of Medical Genetics London: Churchill-Livingston (1997).  2685

Haga clic aquí para ir a la sección de Referencias, 133 Wood J.A., Fishman A.P., Reemtsma K. , y al. A comparison of sweat chlorides and intestinal fat absorption in chronic emphysema and fibrocystic disease of the pancreas N Engl J Med 1959 ;  260 : 951-957  [cross-ref]

Haga clic aquí para ir a la sección de Referencias</sup> First, mutations in the CF gene correlate with specific features of the CF phenotype. These include pancreatic function and the degree of sweat chloride abnormality. Second, genetic background may contribute to the variable manifestations of CF in different populations. Animal models of CF have uncovered modifying genes in different genetic backgrounds that influence phenotype.<sup>101 Rozmahel R., Wilschanski M., Matin A. , y al. Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor Nature Genet 1996 ;  12 : 280-287

Haga clic aquí para ir a la sección de Referencias</sup> Third, environmental factors, such as second-hand exposure to cigarette smoke, have been shown to influence phenotype.<sup>76 Kovesi T., Corey M., Levinson H. Passive smoking and lung function in cystic fibrosis Am Rev Respir Dis 1993 ;  148 : 1266-1271

Haga clic aquí para ir a la sección de Referencias</sup> Accordingly, patients with CF show a wide range in clinical severity, particularly with regard to lung disease.