New tests for fragile X syndrome may simplify diagnosis

Diagnosing fragile X syndrome, the most common cause of mental disability and autism, includes an expensive and complex system of tests. Researchers from NIH have challenged this reality by developing a set of patient screening assays that have the potential to be accurate and less expensive.

Fragile X-related syndrome, also known as Martin-Bell syndrome or Escalante's syndrome, results from expansion of a tract in the FMR1 gene. Those with fragile X syndrome typically have more than 200 repeats. Individuals with 55 to 200 repeats are at risk for fragile X-associated primary ovarian insufficiency and fragile X-associated tremor/ataxia syndrome.

The tests developed by the researchers are capable of amplifying alleles with 1,000 repeats, are sensitive enough to analyze saliva samples and can provide results in less than 24 hours. These change enhance detection of the smallest changes in DNA methylation.

Researchers modified a PCR assay, already capable of sixing small alleles, to size larger alleles.

"Realizing the potential broader utility of the sizing assay, we then expanded its abilities to include both methylation and interruption status. We showed that these assays perform robustly even in the most challenging of situations," wrote lead author Bruce Hayward, PhD, and colleagues.

In the future, researcher hope to incorporate the assays into laboratories to study the events during early embryonic development with the effects of repeat length and methylation status on gene expression and differentiation.

"Without the ability to verify CGG-repeat number and methylation status, it is impossible to distinguish between bona fide developmentally-regulated changes and artifacts arising from the instability in repeat number and methylation commonly associated with these cells," wrote the researchers.