This article has been updated from a previous version to correct the names of the CE platforms used to run Asuragen's assay.
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NEW YORK – The US Food and Drug Administration late on Friday authorized marketing of Asuragen’s AmplideX Fragile X Dx and Carrier Screen Kit, the first genetic test for fragile X syndrome (FXS).
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The assay is intended to aid in diagnosing FXS and is to be used alongside the evaluation of a patient’s family history and clinical signs and symptoms, FDA said.
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The test is also intended for use in adults who may be carriers of genetic alterations in FMR1, the gene associated with FXS.
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According to the US Centers for Disease Control and Prevention, approximately 1 in 4,000 males and 1 in 8,000 females in the US have FXS, a genetic disorder caused by changes in the FMR1 gene located on the X chromosome. A segment of the FMR1 DNA, known as a CGG trinucleotide repeat, is repeated in excess on the X chromosome in individuals with the disorder.
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While some repetition of the CGG repeat is normal, a high number of repeats may indicate potential health risks. Asuragen's test uses a method called triplet repeat primed PCR (TP-PCR) to measure the number of repeats of the CGG segment in the FMR1 gene using a patient blood sample. The test can determine whether the number of CGG repeats is considered normal, intermediate, premutation, or full mutation.
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Individuals with a full mutation typically have FXS, which is associated with developmental delays, learning disabilities, social and behavioral issues, intellectual disabilities, and autism spectrum disorder. Women with a premutation have an increased risk of having a child with FXS, while men with a premutation will pass it to their daughters only. Individuals with normal or intermediate levels of repeated CGG segments are currently thought to be asymptomatic for FXS or other fragile X-associated disorders.
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In addition to aiding in the diagnosis of FXS and for carrier testing, Asuragen's test can be used to help diagnose fragile X-associated disorders, including fragile X-associated tremor/ataxia syndrome, a movement and cognitive disorder that typically occurs in adults over age 50; and fragile X-associated primary ovarian insufficiency, a condition that is characterized by reduced function of the ovaries.
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The FDA said that it reviewed data for the test through its de novo classification program for low- to moderate-risk devices of a new type. The agency evaluated data from two multi-center clinical validation studies conducted across three trial sites to determine that the assay has a diagnostic accuracy of greater than 95 percent. Asuragen noted that carrier screening performance for detection of premutations or full mutations had a positive percent agreement of 100 percent.
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Asuragen had already been marketing AmplideX PCR/CE FMR1 reagents for detecting CGG repeats in the FMR1 gene in a research-use-only capacity. The Applied Biosystems 3500 Dx Genetic Analyzer and 3500xL Dx Genetic Analyzer from Thermo Fisher Scientific, which were FDA-cleared for fragment sizing in parallel with this test, are used to detect the DNA products amplified by TP-PCR. In 2017 Asuragen and Thermo Fisher Scientific began a collaboration around the commercialization of these products.
"AmplideX technology introduced a dramatic paradigm shift in how challenging repetitive sequences, like those within FMR1, could be routinely detected and analyzed," Elizabeth Berry-Kravis, co-investigator of the clinical study and codirector of the molecular diagnostics section of the genetics laboratory at Rush University Medical Center, said in a statement. "Enabling better access to testing to predict and diagnose these cases significantly improves our ability to make a difference in these patients' lives by eliminating the diagnostic odyssey that many families experience and allowing more accurate genetic counseling."