Division of Genetics: Cystic Fibrosis (CF), URMC

Cystic Fibrosis (CF)

Cystic Fibrosis (CF) is a multisystem genetic disease in which defective chloride transport across membranes causes dehydrated secretions. This leads to tenacious mucus in the lungs, to mucus plugs in the pancreas, and to the characteristically high sweat chloride levels. Intelligence and cognitive function are typically normal. More than 25,000 Americans have CF, with approximately 850 individuals newly diagnosed each year. CF is inherited as an autosomal recessive disorder; the responsible gene, the CF transmembrane conductance regulator (CFTR), was mapped to chromosome 7 and identified in 1989.

CF has a highly variable presentation and course. Median age at diagnosis is 6 to 8 months; nearly two-thirds of individuals are diagnosed before 1 year of age. Some individuals have severe pulmonary and/or gastrointestinal disease, whereas others have relatively mild disease with presentation during adolescence and young adulthood. Survival has improved, thus far, through aggressive management of pulmonary, pancreatic, and intestinal complications. Despite advances in treatment, there is no cure for CF.

Treatment

The major goals of traditional treatment of CF are to improve pulmonary, gastrointestinal, and pancreatic outcomes. Pulmonary treatment is focused on physical therapy to decrease obstruction of the airways, antibiotics to decrease colonization by Staphylococcus aureus and Pseudomonas aeruginosa, and nonsteroidal anti-infammatory drugs to decrease the inflammatory cascade and resulting tissue damage. Gastrointestinal and pancreatic treatments include high protein/high caloric diets, pancreatic enzymes, and fat-soluble vitamins. New modalities include the use of inhaled DNase, which breaks down the DNA from neutrophils, and pharmacologic modification of ion transport to loosen secretions. Pharmacologic activation of mutant CFTR protein to stimulate chloride channel activity is being investigated. Double lung transplantation extends life but is not curative.

Epidemiology

CF is one of the most common genetic diseases in Caucasians, with an incidence in the U.S. of about 1 in 3,300.

Group Incidence Carrier
Frequency %
DeltaF508 %
Common
Caucasian
Alleles %
Group
Specific
Alleles Sensitivity

Caucasians 1/3,300 1/29 70 13 - 80

Hispanics 1/8-9,000 1/46 46 11 - 57

Ashkenazi Jews . 1/29 30 67 - 97

Native Americans 1/3,970 . 0 25 69 94

African Americans 1/15,300 1/60-65 48 4 23 75

Asian Americans 1/32,100 1/90 30 . . 30

CF Mutation Analysis

Since the identification of the gene and the major mutation responsible for CF, more than 600 mutations and DNA sequence variations have been identified in the CFTR gene. F508 mutation is represented in almost all populations, although its relative frequency varies among different geographic locations. The highest frequency is observed in Caucasian populations, where it accounts for approximately 70 percent of the CF alleles.

Reference source: Genetic Testing for Cystic Fibrosis. NIH Consensus Statement 1997 Apr 14-16; 15(4): 1-37

Comments/Suggestions to: Mary_True@urmc.rochester.edu