FDA Clears 1st Genetic Test for Fragile X Patients and Carriers

The U.S. Food and Drug Administration (FDA) has authorized the marketing of Asuragen‘s AmplideX Fragile X Dx and Carrier Screen Kit, a first genetic test to help diagnose fragile X syndrome and determine the likelihood of having a child with the condition.

“This novel diagnostic provides doctors and their patients the first FDA authorized genetic test to aid in diagnosing Fragile X Syndrome, as well as helping parents know their risk of having a child with Fragile X Syndrome,” Wendy Rubinstein, MD, PhD, the director of personalized medicine in the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health, said in a press release.

“Early diagnosis is key to helping children affected with Fragile X Syndrome through early intervention,” Rubinstein added.

Fragile X is caused by genetic abnormalities in the gene FMR1, which is located on the X chromosome. Specifically, people with this disorder have an excess amount (over 200) of repetitive sequences known as CGG repeats (C stands for cytosine and G for guanine, two of building blocks of DNA). This so-called “full mutation” leads to no or very little production of the FMRP protein — key to controlling the production of several other proteins at synapses (the sites where nerve cells communicate).

This diagnostic test can determine the number of such repeats in a person’s genes from a blood sample. Depending on the exact number, individual genes can be classified as normal, intermediate, premutation, or full mutation.

People with a premutation in FMR1 have 5 to 200 CGG repeats, and a greater likelihood of having a child with fragile X. Normal and intermediate are generally considered asymptomatic for fragile X or its associated disorders.

The FDA assessed data for this diagnostic test through the de novo classification process, a regulatory pathway for new devices that are unlikely to pose health risks. During this process, the FDA look at information collected at three clinical sites. These data showed that the diagnostic accuracy of the test is over 95%.

The AmplideX Fragile X Dx and Carrier Screen Kit is intended to be used in conjunction with an individual’s family history and symptoms of fragile X. It is not intended as a stand-alone diagnosis tool.

The test is not approved for fetal diagnostic testing, or for testing egg cells obtained for in vitro fertilization.

“The ability to more accurately and reliably measure CGG repeats throughout the expanded range and particularly in the complex premutation zone … represents a tremendous advantage to using the AmplideX Fragile X Dx and Carrier Screen Kit,” said Flora Tassone, PhD, a study co-investigator, and professor at the University of California Davis.

In addition to the authorization, the FDA announced that it is creating new regulatory criteria for this kind of genetic test, which are intended to provide assurances of safety and effectiveness. This creates a new classification to be used to assess similar medical devices in the future.