Cystic Fibrosis

Cystic fibrosis is the most common fatal genetic disease in the United States today. It is estimated that more than 10 million Americans are unknowingly, symptomless carriers of the disease. In addition, the median age of survival for a person with CF is in the mid-30s.

CF causes the body to produce a thick, sticky mucus that clogs the lungs, leading to infection. A secondary effect of CF is blockage of the pancreas which in turn stops digestive enzymes from reaching the intestines where they are required to digest food. Furthermore, the severity of the disease symptoms of CF is directly related to the characteristic effects of the particular mutation or mutations that have been inherited.
Additional Background Info by NCBI Genes and Disease

THE AFFECTED GENE

Cystic fibrosis, which afflicts about 1 in 2000 Caucasians, is caused by an autosomal recessive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The defective gene codes for a chloride transporter found on the surface of the epithelial cells that line the lungs and other organs. The result is the defective transport of chloride, and secondarily sodium, by epithelial cells. Thus the amount of salt is increased in bodily secretions.

Collection of CFTR-Related Information

GENE VIEW FOR CYSTIC FIBROSIS

Gene location of CFTR

Chromosomes 7

Master Map and Ideogram

THE HOMOLOGS

Conserved Domain 0f the 1480 aa CFTR as aligned with 36 Unique Species!
Notice the extrodinary similarities between species...

USING PCR AMPLIFICATION AND THE KNOCKOUT TECHNIQUE TO STUDY CF

In one reported case, a couple who where both carriers of CF, had their fertilized human embryos screened in vitro. The DNA was then isolated from a single embryonic cell and subjected to PCR and then analyzed for mutations identified in one of the two copies of chromosome 7 in each parent. In this way embryos that had inherited the wild-type chromosome from at least one parent were identified and then transferred to the mother's uterus. So by using this procedure, carrier couples can be assured of having children that will not be at risk for cystic fibrosis. learn more about this DNA screening technique at GenBook

Recent studies on cystic fibrosis illustrate the use of the knockout technique. Using the human gene, researchers isolated the homologous CFTR mouse gene and subsequently introduced mutations in it. The gene-knockout technique was then used to produce homozygous mutant mice, which showed symptoms similar to those of humans with cystic fibrosis. Knockout mice are currently being used as a model system for studying this genetic disease and developing effective therapies. Click on this link to learn more about the fascinating research on these mice

Multidrug Resistance of the CFTR Protein: A Problem for Biomedical Companies and Doctors

Multidrug resistance is the phenomenon by which the development of resistance to one drug by a targeted cell also makes the cell less sensitive to a range of other compounds.

The onset of multidrug resistance was found to correlate with the expression and activity of the CFTR membrane protein. This protein acts as an ATP-dependent pump that extrudes a wide range of small molecules from cells that express it. Thus, when CF cells are exposed to a drug, the CFTR pumps the drug out of the cell before the drug can exert its effects.

STRUCTURAL ANALYSIS OF THE CFTR PROTEIN

In addition, biochemical analysis of the amino acid sequences of the human CFTR protein and homologous CFTR proteins revealed a common architecture. Each protein comprises four domains: two membrane-binding domains of unknown structure and two ATP-binding domains.

TREATMENT FOR CF

The treatment of CF depends upon the stage of the disease and the organs involved. Clearing mucus from the lungs is an important part of the daily CF treatment regimen.

Chest physical therapy is a form of airway clearance done by vigorous clapping on the back and chest to dislodge the thick mucus from the lungs.

Pulmozyme® is a mucus-thinning drug shown to reduce the number of lung infections and improve lung function.

Approximately 90 percent of all people with CF take pancreatic enzyme supplements to help them absorb food in digestion.

Latest Treatment for Cystic Fibrosis Patients: The Aztreonam Lysinate Inhaler (an electronic aerosolized antibiotic)

Studies show that aztreonam lysinatefor worked to decrease the bacteria, Pseudomonas aeruginosa, that is a common source of infection in the lungs of people with CF.
Why Aztreonam ?









Related CF Articles by PubMed

Three autopsied cases of cystic fibrosis in Japan.

The incidence of cystic fibrosis (CF) is very rare in Japanese, while it is frequent in Caucasians. Here we report on three Japanese cases of CF.
However the most frequent mutation associated with CF in Caucasians, was not found in these patients. This article reviews 22 Japanese autopsied cases of CF and examines the common symptoms as they relate to the symptoms of Caucasians with CF. "The high incidence of meconium ileus (an intestinal obstruction) in Japanese CF patients may relate to a clinically severe phenotype and reflect a different genetic background between Caucasians and Japanese." (Iwasa, S. et. al 2001)

CF and Typhoid Fever....The Heterozygous Advantage

Role of the cystic fibrosis transmembrane conductance regulator in innate immunity to Pseudomonas aeruginosa infections

By Gerald B. Pier

In addition to being a receptor for epithelial cells in the lungs, CFTRs are also receptors for gastrointestinal epithelial cells for Salmonella enterica serovar Typhi, the etiologic agent of typhoid fever. In a recent study using transgenic mice, there was a significant decrease in translocation of this form of salmonella to the gastrointestinal submucosa in transgenic mice that are heterozygous carriers of a mutant F508 CFTR allele (the most common mutation in the CFTR). This suggests that heterozygous CFTR carriers may have increased resistance to typhoid fever. This shows a possible heterozygote advantage for carries of mutant alleles of CFTR.

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