New genetic test is a better predictor of risk of having a child with fragile X syndrome

Molecular diagnostics company Asuragen, Inc., has announced study results 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, a common inherited cause of intellectual disability and autism. The 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 the syndrome.

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, intermediate, pre-mutation, and full mutation.

“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,” says Gary Latham, PhD, Vice President of Research and Technology Development at Asuragen. “Xpansion Interpreter predicts the risk of CGG expansion by identifying the presence of another unique DNA sequence in the gene that acts as a stabilizer in the string of CGG repeats and protects against expansion.”

The study evaluated AGG interruptions in 457 mother-to-child transmissions in women with intermediate or small pre-mutation fragile X alleles (45 to 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. Read a study abstract.