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Study Finds New Genetic Test Better Predicts Mother's Risk of Having a Child With Fragile X Syndrome

March 21, 2013

Fragile X syndrome is the most common inherited cause of intellectual disability and autism

Data on Asuragen's Xpansion Interpreter® Test published in American Journal of Medical Genetics

Austin, Texas – March 21, 2013 – Asuragen Inc., a leading molecular diagnostics company, today announced results from a study demonstrating that a new molecular test called Xpansion Interpreter® can improve the determination of a woman's risk of having a child with fragile X syndrome, the most common inherited cause of intellectual disability and autism, compared to existing risk measures. The Xpansion Interpreter Test is based on a technology breakthrough that reveals both the number and position of “interrupting” DNA sequences in the fragile X gene of the mother and more accurately estimates the likelihood that her child will have fragile X syndrome. The study will be published in the April issue of the American Journal of Medical Genetics and presented today at the 2013 American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting in Phoenix, AZ.

“The increased testing of women for fragile X status has led to the identification of carriers whose risk of having a child with fragile X syndrome is unknown,” said Sally Nolin, Ph.D., Director of the Fragile X Laboratory at the New York Institute for Basic Research in Developmental Disabilities and lead author on the paper. “We are now able to better estimate this risk so that women who are fragile X intermediate or premutation carriers can be counseled with the best possible information.”

Fragile X syndrome is caused by a mutation in the FMR1 gene that alters the production of a protein required for normal brain development. The mutation is the result of a small part of the genetic code (CGG) being repeated on a fragile area of the X chromosome. Repeat CGG sequences are categorized into four classes based on repeat length: normal (<45 repeats); intermediate (45-54 repeats); premutation (55-200 repeats); and full mutation (> 200 repeats).

“A mother with more than 55 CGG repeats in her fragile X gene may be perfectly normal, yet instability of this gene can result in fragile X syndrome in her child,” said Gary Latham, Ph.D., Vice President of Research and Technology Development at Asuragen. “Xpansion Interpreter predicts the risk of CGG expansion in the child by identifying the presence of another unique DNA sequence in the gene – an AGG sequence – that acts as a stabilizer in the string of CGG repeats and protects against expansion.”

The published study, performed in collaboration with the New York Institute for Basic Research in Developmental Disabilities, Rush University Medical Center, Emory University School of Medicine and the M.I.N.D. Institute at the University of California Davis, evaluated AGG interruptions in 457 mother-to-child transmissions in women with intermediate or small premutation fragile X alleles (45-69 CGG repeats). The results revealed that the number and position of AGG interruptions, coupled with total number of CGG repeats, provide significant improvements over current risk estimates in predicting fragile X gene instability and expansion to a full fragile X mutation. All nine transmissions of the full fragile X expansion mutation in the study were from mothers with CGG repeat regions lacking AGG sequences.

“The difference in expansion risk for premutation carriers without any AGG is much higher than those with one or two AGGs,” said Dr. Nolin. “Our study demonstrates that women with 50-54 repeats and no AGG interruptions may expand to larger, premutation alleles. In addition, there is a clear risk of fragile X syndrome in the children of women with small premutation alleles without AGG. These women should be offered the option of fragile X prenatal testing.”

The Xpansion Interpreter® Test is made available through Asuragen's accredited clinical laboratory in Austin, TX. Asuragen developed the methods and process to overcome formidable technological challenges and make FMR1 genotyping efficient and AGG sequence mapping accurate for use in clinical practice.

“AGG profiling complements our AmplideX® fragile X PCR technologies that also offer unprecedented sensitivity in detecting fragile X mutations, and the ability to determine methylation status of each FMR1 allele without the need for Southern blot analysis,” said Rollie Carlson, Ph.D., President & CEO of Asuragen. “Our experience and technological capability have made Asuragen an industry leading provider of solutions for fragile X profiling.”

About Asuragen

Asuragen is a molecular diagnostics company with a pioneering position in miRNA using genomics to drive better patient management through best-in-class clinical testing solutions. The company uses a breadth of technologies and talent to discover, develop and commercialize diagnostic products and clinical testing services with efficiency and flexibility both internally and for our companion diagnostic partners. Today, Asuragen's products, services and technologies drive countless patient management decisions across oncology, genetic disease and other molecular testing modalities. In the future, we envision the Company's development of miRNA-based clinical diagnostics will help transform medicine by improving clinical outcomes and health economics.