Cystic Fibrosis (CF) is caused by an autosomal recessive mutation of the cystic fibrosis transmembrane regulator gene (CFTR), which was identified via positional cloning. Cystic fibrosis is due to abnormal fluid and electrolyte transport across epithelial apical (pointed) membranes. This leads to disease of the lung, pancrea, intestine, hepatobiliary tree and male genital tract. Noticeable when kissing a baby with cystic fibrosis, loss of CFTR activity leads to chloride and sodium build-up in sweat glands. Also, the mucous layer of the lung becomes 'sticky' and traps pathogens, leading to chronic pulmonary infections..
The first sign of cystic fibrosis is usually high concentration of sodium and chloride in sweat. The average patient survives to ∼33 years, eventually succumbing to chronic lung and heart infections, and maldigestion due to a deficiency of pancreatic enzymes. Many males are infertile due to absence of a vas deferens; most females have near-normal fertility. Postnatal lower intestinal tract obstruction also may occur, treatable by surgery. Some individuals with mutations in the CFTR may have just one or all of these phenotypes.
Approximately 2% of white (European) populations carry a cystic fibrosis disease allele, although carriers are almost nonexistent in other populations. The most frequent CFTR defect is δF508, a missense mutation that reduces ATP binding and accounts for 70% of all CF alleles in white populations. Patients homozygous for δF508, or with premature stop codons in CFTR all have insufficient pancreatic activity, but differing pulmonary (lung) disease. Two alleles of a modifier gene encoding transforming growth factor β1 (TGFβ1) are frequent in cystic fibrosis patients with severe pulmonary disease. Also, a cystic fibrosis genocopy (aka phenocopy -- an identical phenotype for different genetic reasons) is a mutation in SCNN1, which encodes an epithelial sodium channel. With ∼85% of CFTR disease alleles identified, DNA diagnosis is useful prenatally and to identify carriers amongst relatives of a patient with no familial history of cystic fibrosis. However, the only current treatments for cystic fibrosis are antibiotics, exercise and a nutritious diet.