CLINICAL CASES
77
CFTR: Cystic fibrosis transmembrane conductance regulator; a ligand-
gated chloride channel that is regulated by phosphorylation. It is a mem-
ber of the adenine nucleotide binding cassette (ABC) family of transport
proteins.
Electrophoresis: The technique by which charged molecules in solution
are separated in an electric field according to their different mobilities in
the supporting medium.
Gel electrophoresis: Electrophoresis using a gel as the supporting medium.
Common gels are polyacrylamide and agarose.
Northern blot: The technique by which molecules of ribonucleic acid
(RNA) are separated by gel electrophoresis, transferred to a membrane
support, and incubated with labeled oligonucleotide probes. Specificity
is obtained by using oligonucleotide probes that have sequences com-
plementary to the target RNA.
Southern blot: The technique by which molecules of DNA are separated
by gel electrophoresis, transferred to a membrane support, and incubated
with labeled oligonucleotide probes. Specificity is obtained by using
oligonucleotide probes that have sequences complementary to the target
DNA.
Western blot: The technique by which protein molecules are separated by
gel electrophoresis, transferred to a membrane support, and incubated
with labeled antibodies. Specificity is obtained using antibodies that will
bind the protein molecule of interest.
D ISC U SSIO N
Cystic fibrosis is the most common lethal autosomal recessive disease affect-
ing the Caucasian population. It has a frequency of approximately 1 in 2500
and a carrier frequency of approximately 1 in 25. The protein affected is the
cystic fibrosis transmembrane conductance regulator (CFTR), which is a chlo-
ride ion channel. There are over 1000 mutations that have been discovered
in the CFTR gene and over 80 percent of these mutations lead to disease.
The mutations lead to (1) defective or decreased protein production, (2) defective
processing of the protein, (3) protein that is defective in the regulation of the
chloride channel, or (4) defect in the transport of chloride ions. The most com-
mon mutation, a deletion of a phenylalanine residue at amino acid position
508 (AF508), results in misfolding of the protein; it consequently does not traffic
to the membrane.
Defects in the CFTR decrease the ability of cells to transport Cl- in a num-
ber of tissues, particularly the pancreas, airway epithelia, and sweat glands.
When Cl- transport is defective in the pancreas, it leads to decreased HCO3-
secretion and decreased hydration that leads to thick secretions that block the
pancreatic ducts and destruction of the organ. In the lungs, the decreased
absorption of Cl- ions is thought to increase the absorption of the airway sur-
face liquid thus increasing the viscosity of mucous, decreasing mucociliary
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