Advanced Genetic Testing for Cystic Fibrosis

Is It Worth the Cost?

Basic genetic testing panels are effective in detecting many mutations of the gene, but the standard test is not foolproof as it only tests for the most common CFTR mutations. In some situations, more thorough genetic testing could be beneficial.

Who Are Some People That Might Benefit From Advanced Testing?

1. Asians, Hispanics, African-Americans or people of mixed race.

   Why?
   Many of the CFTR mutations that commonly occur in these populations are not included in the basic 23-mutation testing panel.

2. People who have symptoms of CF, or had a positive newborn screening test, but basic genetic testing panel did not detect any mutations.

   Why?
   This person may have a less common mutation of the CFTR gene that was not included in the 23-mutation panel.

3. People who know they have a rare CF mutation in their family history.

   Why?
   This person is at higher risk of also having a mutation that would not be detected by the 23-mutation panel.

Who Are People That Probably Don’t Need Advanced Testing?

1. Anybody who has already had two mutations of the CFTR gene detected by the basic testing panel.

   Why?
   This person has a common mutation and has already been diagnosed with cystic fibrosis. Further testing would not provide any further information.

2. People of Ashkenazi Jewish descent.

   Why?
   The basic 23-mutation testing panel detects 94% of the mutations that occur in this population and is likely to be sufficient. However, if the basic panel is negative but there is family history or symptoms of CF disease, advanced genetic testing could be beneficial.

Advanced Testing Options

In the U.S., two major nationwide genetic laboratories offer advanced testing for cystic fibrosis. Like the basic tests, these tests require a physician’s order. They are more expensive than standard mutation tests, and might not be covered by insurance. The specimen is collected at a local lab and sent to the specialty lab’s nearest location for processing. Results will take longer than tests done at a local or regional lab.

Genzyme
Genzyme offers two advanced genetic tests for cystic fibrosis:

1. CFplus Mutation Analysis: Just like the basic testing panel, this test looks for specific mutations. The CFplus Analysis adds 74 less common mutations to the 23-mutation panel, for a total of 97 mutations. Genzyme reports that their panel detects 90% of the CFTR mutations in Caucasians, 81% in African-American, and 78% in Hispanic populations. The test can be done on blood, mouthwash, or cheek swab and takes 5-8 days to process once Genzyme receives the specimen.
2. Cystic Fibrosis Gene Sequencing: Unlike mutation panels, which look for the presence of certain mutations, gene sequencing looks at the entire composition of the gene to find out what codes are present. Gene sequencing is expensive, but detects about 98% of CF mutations. The test requires a blood specimen, and results may take up to three weeks.

Ambry Genetics
Ambry offers an advanced testing option, often called the “Ambry Test,” which is a blood test that is done in steps to help control costs:

1. 508 First: The first step of the Ambry test looks specifically for the Delta F508 mutation, which is the most common mutation of the CFTR gene. If Delta F508 is detected, no further information is needed and the testing stops. This part of the test takes less than a week to complete.
2. CF Amplified: If Delta F508 is not detected in the initial stage of testing, the next step is gene sequencing. Ambry reports that their CF Amplified test is more effective than standard gene sequencing tests because they take the testing a step further and look for deletions, or missing parts, of the CFTR gene. Results may take up to 5 weeks for this test.

_{Sources:
American College of Medical Genetics. “Cystic Fibrosis Population Carrier Screening: 2004 Revision of American College of Medical Genetics Mutation Panel”. 2004. Genet Med 6:5:387-391. 11 July 2008.
“The Ambry Test: CF AMPLIFIED™Ambry Genetics”. Ambry Gentics. 2006. http://www.ambrygen.com.
“CFplus™ Cystic Fibrosis Mutation Analysis.” Information Brochure. Genzyme Corporation. 2006. http://www.genzymegenetics.com.}