Is Expanded Mutation Testing Practical for CF Carrier Screening?

A new study questioned the value of expanded genetic testing for cystic fibrosis.

The findings suggested that expanded panels might promote ill-informed decisions and anxiety for physicians and couples seeking testing to determine their risk of passing the disease to their children.

Testing for genetic mutations beyond those medically recommended is unlikely to prevent the birth of children with classic cystic fibrosis and may detect mutations causing only mild disease, according to an eight-year study performed by scientists at Quest Diagnostics (Madison, NJ, USA).

Participants in the study came from an ethnically diverse American population. It involved analyses of more than three million deidentified test results performed by the company's laboratories over an eight-year period ending in April 2010.

The company's scientists found that CF testing, using 23 recommended mutations plus an additional eight to nine clinically validated mutations performed for patients in its labs, identified nearly 100 % of carriers among Caucasians, including Ashkenazi Jews, the highest risk group for CF, as compared to well-established estimated carrier rates. The CF testing also performed comparably to the American College of Obstetricians and Gynecologists (ACOG; Washington DC, USA) predictions for performance in detecting carriers in African, Hispanic, and Asian Americans.

In 2004, the American College of Medical Genetics (ACMG; Bethesda, MD, USA) and ACOG recommended physicians offer panels based on the 23 recommended mutations to couples to help identify carrier status. Despite the guidelines, expanded test panels that identify dozens up to nearly 100 nonguideline recommended mutations are widely offered by certain laboratories in the US.

The study findings appear online in the journal Genetics in Medicine.

"This outstanding study should finally put to rest the continuing debates and misinformation that suggest more mutations are always better when it comes to cystic fibrosis carrier screening," said Wayne W. Grody, MD, PhD, professor in the departments of pathology and laboratory medicine, pediatrics, and Human Genetics at the UCLA School of Medicine (Los Angeles, CA, USA). Dr. Grody led one of the influential NIH-funded pilot studies on CF carrier screening and cochaired the ACMG committee that developed the recommended core mutation-screening panel. He is not affiliated with the study or with Quest Diagnostics.

Related Links:
Quest Diagnostics
American College of Obstetricians and Gynecologists
American College of Medical Genetics
UCLA School of Medicine