Mild pulmonary, but severe hepatic disease in a cystic fibrosis patient homozygous for a frameshift mutation in the regulatory domain of the CFTR

The clinical phenotype of cystic fibrosis (CF) patients is very variable and it has been suggested that patients lacking the cystic fibrosis transmembrane conductance regulator (CFTR) have milder lung disease than those having an altered CFTR. However, on the basis of the large variation in lung function in patients homozygous for the most common CF mutation, Delta F508, and W1282X homozygotes, it was concluded that most CF patients have a common phenotype, but that other genetic and environmental factors may be important for the clinical phenotype. We describe a patient, homozygous for a frameshift mutation in the regulatory (R) domain of the CFTR, who presented with mild lung disease but severe hepatic and pancreatic involvement.