Abstract
Cystic fibrosis (CF) is a simple, autosomal recessive disorder caused by mutations in CFTR, encoding the CF transmembrane conductance regulator1, 2. The molecular defects resulting from over 800 different mutations in CFTR only partially explain the clinical heterogeneity of the disease.
While most CF patients suffer from pancreatic enzyme insufficiency, 10-15% of patients have a pancreatic-sufficient phenotype, which has been correlated with a group of mild CFTR mutations3 characterized by their ability to confer residual chloride-channel function. Meconium ileus (MI) is a severe intestinal obstruction detected in a subset (15-20%) of CF patients at birth.
Although MI usually occurs in patients with pancreatic insufficiency, no specific CFTR mutations have been found to determine MI (refs 3,4). A familial recurrence rate of 29% suggests that other genetic factors are involved in the expression of the MI phenotype5.
No independent correlation between CFTR genotype and CF lung disease has been described, indicating that the extreme variability in the lung phenotype is also determined by modifier genes and environmental factors.