Clinlab Navigator

Cystic Fibrosis

Approximately 30,000 individuals living in the United States have cystic fibrosis (CF). Cystic fibrosis is the most common life-limiting autosomal recessive genetic disorder in Caucasians, with an incidence of 1 in 3000 newborns. The disease is less common in other ethnic groups as seen in the following table. 


Ethnic Group Carrier Disease
European Caucasian 1:29 1:3,300
Ashkenazi Jewish 1:29 1:3,300
Hispanic American 1:46 1:8,500
African American 1:65 1:15,300
Asian American 1:90 1:32,100


Cystic fibrosis is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which codes for a protein that serves as a chloride ion channel in epithelial cell membranes. The CFTR protein is expressed on the apical membranes of epithelial cells in the trachea, bronchi, pancreas and sweat glands. CFTR selectively conducts chloride and facilitates transport of bicarbonate. In general, CFTR mutations result in reduced quantity or function of CFTR protein at the cell surface. Affected cells are impermeable to chloride conductance, leading to increased sweat chloride concentration, highly viscous mucus and organ damage from ductal inspissation. Progressive airway destruction is the predominant cause of morbidity and mortality.

CF is an autosomal recessive disease. People with CF inherit a mutation in the CFTR gene from each parent. More than 1,700 mutations, in the CFTR gene have been associated with CF. More than 1600 CFTR variants have been reported; most of which are rare. The F508del mutation results in no functional expression of CFTR and accounts for 70% of cystic fibrosis cases in the Caucasian population.

Mutations that result in some residual chloride transport function are often associated with milder disease. More widespread screening of individuals in recent years has led to the realization that the clinical spectrum of disease caused by CFTR mutations is much broader than originally thought. Approximately 2% of adults present with atypical or mono-symptomatic disease including chronic bronchitis, sinusitis with nasal polyposis, male infertility due to obstructive azoospermia or chronic pancreatitis.

Laboratory tests for CFTR dysfunction include sweat chloride testing and molecular testing for CFTR mutations. DNA testing is used for further investigation of patients with intermediate sweat chloride results. Some experts also recommend DNA analysis in individuals with positive sweat testing for prognostic and epidemiologic purposes.

DNA testing is also helpful in determining if a patient is a candidate for targeted therapy. Specific drugs are now available for CF caused by a few mutations. In 2012, FDA approved ivacaftor (Kalydeco) which works in the roughly 4 percent of CF patients who have the G551D mutation, along with others who have one of 23 relatively rare mutations that result in partially functioning CFTR. In 2015, FDA approved the combination of ivacaftor with lumacaftor for patients with two copies of the F508del mutation.

Molecular diagnosis is usually carried out by direct mutation analysis. Most diagnostic laboratories in the United States screen for at least 23 of the most common mutations, using a panel developed for population screening by the American College of Medical Genetics (ACMG).


DF508 R117H 711+1G>T
DI507 1717-1G>A 1898+1G>A
G542X A455E 2184delA
G551D R560T 1078delT
W1282X R1162X 3849+10kbC>T
N1303K G85E 2789+5G>A
R553X R334W 3659delC I148T
621+1G>T R347P 3120+1G>A


Because this panel is limited, some carriers will not be detected. The detection rate of this panel varies with ethnicity.  The following table lists the detection rate of the panel and the remaining carrier risk for an individual who has a negative result.


Ethnic Group Detection Rate (%)

Risk before Test

Risk after negative test
European Caucasian 80 1:29 1:140
Ashkenazi Jewish 97 1:29 1:930
Hispanic American 57 1:46 1:105
African American 69 1:65 1:207

Asian American

30 1:90 1:125


In a diverse ethnic population, a panel of 40 mutations that includes CFTR mutations found to be more prevalent in non-European ethnicities is recommended. W1282X mutation is most common in Ashkenazi Jews. The highest risk of pancreatic insufficiency is associated with DF508, G542X, G551D, N1303K and W1282X mutations.  The R117H mutation is associated with both cystic fibrosis and congenital bilateral atresia of the vas deferens. 

A diagnosis of CF is confirmed if two CF-causing mutations are detected and the sweat test is intermediate or positive. For individuals with an intermediate or positive sweat chloride test result but in whom two mutations are not detected by the standard mutation panel, more extensive testing should be undertaken.

The American College of Medical Genetics (ACMG) and the American College of Obstetrics and Gynecology (ACOG) recommend that all Caucasian couples who are pregnant or are considering pregnancy be offered carrier screening for cystic fibrosis. They also recommended that non-Caucasian couples be made aware of the availability of screening. The rationale for these recommendations is that carrier detection allows for earlier identification of at risk couples who would then have the ability to exercise their reproductive options, including prenatal diagnosis and earlier treatment of affected children.   

Screening may be performed either before pregnancy or during the first trimester. Preconception screening is preferable.  Screening of both partners can be accomplished either concurrently or sequentially.  Concurrent screening of both partners is recommended for Caucasians and Ashkenazi Jews.  This provides a more rapid and precise estimate of carrier status and the risk of cystic fibrosis in their offspring.  Sequential screening is the screening of one partner followed by screening of the second partner only in the event of a positive result in the first partner.  Since most individuals test negative, this strategy is less expensive but takes longer.  Also, since the screening tests are not 100% sensitive, there is a higher residual risk when only one partner is tested and found to be negative and the carrier status of the other partner remains unknown. The following table shows the risk of an infant being affected by cystic fibrosis if one or both parents test negative. 

Ethnic Group One Negative Both Negative
European Caucasian 1:140 1:78,400
Ashkenazi Jewish 1:930 1:3,459,6000
Hispanic American 1:105 1:44,100
African American 1:207 1:171,396
Asian American 1:125 Unknown
AddThis Social Bookmark Button