Asuragen’s Xpansion Interpreter® Test Study of 1,040 Transmissions of Fragile X Alleles

Asuragen, Inc. has announced a collaborative publication with scientists at the New York Institute for Basic Research in Developmental Disabilities that describes the most comprehensive study to date examining the relationship between AGG sequence interruptions and the risk of triplet repeat expansion in the fragile X gene, FMR1.

The publication, titled “Fragile X Full Mutation Expansions are Inhibited by One or More AGG Interruptions in Premutation Carriers” assessed 1,040 parent-to-child transmissions of intermediate and premutation-sized fragile X alleles from 705 families and is available online in Genetics in Medicine, a leading translational genetics journal published by the American College of Medical Genetics.

The FMR1 molecular analyses reported in the study were enabled using a fragile X technology pioneered by Asuragen and commercialized as Xpansion Interpreter® in the company’s CAP-accredited CLIA laboratory.

Approximately 1 in 200 women and 1 in 400 men are fragile X carriers and have a risk of transmitting an expanded fragile X gene to their child. Although transmission of a premutation allele is associated with a range of clinical presentations, including fragile X primary ovarian insufficiency (FXPOI), age-onset fragile X-associated tremor/ataxia syndrome (FXTAS), and variable penetrance, the most severe clinical consequences arise in fragile X syndrome (FXS), which is associated with full mutation expansions.

FXS is the most common known genetic cause of autism and the leading cause of inherited intellectual disability. In addition to learning deficits, children with FXS also have speech/language delay and seizures and are commonly diagnosed with ADHD or clinical anxiety.

“Our study demonstrates that AGG sequences are critical ‘stability anchors’ in the fragile X CGG repeat tract. By extending our previous work to include parent repeat sizes up to 90 CGG, we were able to show that AGG interruptions can alter the risk of full mutation expansion by more than 10-fold for individuals with same number of CGG repeats,” commented Dr. Sally Nolin, Director of the Fragile X Laboratory at the New York Institute for Basic Research in Developmental Disabilities and lead author on the publication. “In addition, since more than half of our study cohort was drawn from patients identified by population screening, rather than families with a history of fragile X, our results should be generally applicable to fragile X carrier screening.”

The vast majority of the estimated 1 million fragile X carriers in the US are undiagnosed. However, rapid growth in carrier screening programs that can identify common disease alleles, such as those associated with FXS, cystic fibrosis, and Tay-Sachs disease, has led to increasing rates of carrier detection for multiple genetic disorders and, with it, opportunities to provide individualized information that can help educate patient decisions. The results of Asuragen’s collaborative study personalizes risk assessments for fragile X carriers through insights gleaned from the detection of AGG interruptions within the CGG repeat element of the FMR1 gene.

“This large, well-powered study offers further evidence of the value of AGG sequence information in providing more accurate and personalized expansion risks for fragile X carriers,” said Dr. Matthew McManus, President and CEO of Asuragen. “The Xpansion Interpreter® Test has been, and continues to be, the only validated diagnostic technology for delivering reliable AGG results to providers and patients.”