Chicago Center for Jewish Genetics Disorders - Ashkenazi Disorders: Cystic Fibrosis

Ashkenazi Disorders: Mendelian

Gene: The gene involved in cystic fibrosis is the cystic fibrosis transmembrane conductance regulator (CFTR), located at 7q31.2. It encodes a protein that controls the flow of chloride ions into and out of specific cells. More than 1,000 mutations in this gene have been reported so far, many of which are rare.

Mutations and testing: The W1282X mutation represents 60% of mutant alleles seen in Ashkenazi Jews with cystic fibrosis. Due to the large number of mutations known, there is debate as to how many and which mutations should be included in the testing panel. The detection rate increases minimally after testing for the 10 to 15 most common mutations in any given population group. In the Ashkenazi Jewish population mutant allele detection rates vary from 95% to 97% depending upon which mutations are included in the testing panel.

Traits: Cystic fibrosis affects three main organ systems: respiratory, gastrointestinal, and reproductive. Respiratory manifestations include pulmonary obstruction by thick mucus and infection of the epithelia. Recurrent pneumonias and colonization with pseudomonas species are common. The chronic lower airway inflammation and endobronchial damage leads to fibrosis of the lung parenchyma and is the major cause of morbidity and mortality seen in cystic fibrosis. Gastrointestinal problems include exocrine pancreatic insufficiency, which occurs in the majority of patients, and neonatal meconium ileus, which occurs in 10-20% of newborns with cystic fibrosis. Diabetes mellitus develops in over 17% of adults with cystic fibrosis. Infertility occurs in 95% of males with cystic fibrosis due to congenital absence of the vas deferens (CBAVD) and azoospermia. Individuals with cystic fibrosis have elevated sweat electrolyte levels, which can be used for diagnostic testing. Cystic fibrosis is nearly always fatal by the fourth decade of life.

Treatment: Respiratory treatment consists of constant surveillance, antibiotics, anti-inflammatory agents, mucolytic agents, and chest physiotherapy. Gastrointestinal treatment consists of special formulas and supplemental feedings for weight gain, fat soluble vitamins, and pancreatic enzyme replacement. Infertility in males has no treatment but some advanced reproductive techniques may be possible in the future.

Other:

Pregnancy is possible depending upon the severity of pulmonary disease and nutritional status of the mother. If these are mild to moderate, risk factors for deteriorating health and early death after pregnancy are the same as the for general adult female population. The risk for congenital anomalies is not increased and breast feeding is considered safe.
As of October 2001, the American College of Obstetrics and Gynecology considers cystic fibrosis carrier screening to be standard of care for Ashkenazi Jewish couples. It should be offered to all persons of Ashkenazi Jewish descent who are pregnant or planning a pregnancy.
Newborn screening for cystic fibrosis is now offered in some states.
Men may have no symptoms of cystic fibrosis other than infertility due to CBAVD. CBAVD occurs in 95% of males with a diagnosis of classic cystic fibrosis. In healthy males with CBAVD, about 60 to 75% have been found to have cystic fibrosis mutations.

Cystic Fibrosis from Geneclinics.org
http://www.genetests.org/profiles/cf

Reviewed by Joel Charrow, MD, Head, Division of Genetics, Birth Defects and Metabolism, Children’s Memorial Hospital, 8/07.

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This page last updated on September 7, 2007.