Genotype-phenotype correlation in cystic fibrosis patients.

Cystic fibrosis (CF) is the most common severe recessive disease in Caucasians. The gene responsible for the disease encodes a protein named cystic fibrosis transmembrane conductance regulator, which is predicted to function as a cAMP-regulated chloride channel. Reduced chloride secretion is at the basis of insufficient hydratation of ductural mucus in the airways, reproductive system and pancreas, leading to progressive obstructive damage. The clinical expression of the disease is heterogeneous but most CF patients typically present with chronic obstructive lung disease, elevated electrolyte concentration in sweat and insufficient pancreatic exocrine function. Approximately 10-15% of CF patients have pancreatic sufficiency, 2 to 5% of patients have liver disease and infertility is present in almost all adult males, due to congenital bilateral absence of the vas deferens, and frequently in females. To date, over 500 mutations have been identified in the CFTR gene. A genotype-phenotype correlation has been observed only with pancreas status, while severity of lung involvement is not clearly related to the CFTR genotype, suggesting that this phenotype might be modulated by additional genetic or environmental factors; liver disease in general is not genetically determined. A large proportion of sterile healthy men with congenital bilateral absence of the vas deferens carry a mutation in at least one of their CFTR genes. The data collected so far suggest that the relationship between the CFTR genotype and the clinical manifestation is multiple and complex.