U.S. couples looking forward to parenthood and parents of newborns and infants have a new diagnostic test option: a screening test to detect cystic fibrosis (CF) in children and identify parents-to-be who are carriers. The Tag-It test, manufactured by Tm Bioscience Corporation (Toronto, Canada), was approved by the U.S. Food and Drug Administration (FDA) in early May 2005. Although other genetic tests for CF are being manufactured and widely used, this is the first DNA-based blood test for CF to be approved by the FDA.

A “partial panel” test, the Tag-It test can be used to identify adults who are carriers, as an aid in newborn screening, and to confirm a diagnosis in infants and children. It cannot, however, predict the severity of the disease. The test is too limited to use alone to diagnose CF and is not intended for fetal or preimplantation testing.

In 2001, the American College of Medical Genetics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG) recommended that obstetricians nationwide offer preconception and prenatal carrier screening for CF to all patients, regardless of race, ethnicity, or demographics. This was in response to a 1997 recommendation by the National Institutes of Health for population-wide screening for CF. Since then, laboratories have seen a huge increase in CF screening.

It is best to screen for CF carrier status in parents-to-be during preconception planning or as early as possible in a pregnancy and then in the newborn. CF screening helps prospective parents know if they are carriers and if their unborn child is at risk for the disease. A CF screen of an infant can also help new parents provide the best health care and supportive environment for children who have the disease but don’t yet show symptoms; early intervention has been shown to improve outcomes for these patients. More than a dozen states offer CF testing as part of their newborn screening tests.

There are more than 1,300 known mutations of the cystic fibrosis transmembrane regulator (CFTR) gene that may contribute to the disease. In 2001, ACOG set a minimum standard that tests should screen for the 25 most common mutations of the CFTR gene plus a few variations. “Partial panel” tests usually identify 80% to 90% of Caucasian carriers, depending on how many of the mutations are included; the sensitivity of a partial-panel test is generally even greater for Ashkenazi Jews, but quite a bit lower for those of Hispanic, African, or Asian descent because of the different mutation frequencies within each of these ethnic groups. With the Tag-It 40+4 test, laboratories can detect 40 mutations and 4 variants—the most common mutations plus additional mutations prevalent in North America and elsewhere. The test screens for all the mutations recommended by ACOG and ACMG.

Because all the mutations are not evaluated in partial-panel screening tests, however, failure to identify a mutation does not equate to zero risk. There is still a slight chance the individual has a rare mutation that was not part of the panel. For those at high risk or in situations in which a higher degree of confidence is required, a more comprehensive test can be appropriate. Other tests are available that analyze the entire gene, looking for all the mutations and catalogued variants and raising the detection rate to 99%. Individuals interested in CF carrier status screening should speak with their healthcare provider and/or a genetic counselor for more information.

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Tm Bioscience receives FDA clearance for cystic fibrosis DNA test (press release, PR Newswire US). May 9, 2005. On the Internet at the Web site of the Boomer Esiason Foundation: http://www.esiason.org/article.php?wh=88. Accessed June 1, 2005.

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