Blood Test Sheds Light on Fragile X Syndrome

A blood test may shed new light on Fragile X syndrome related disorders in women, as Fragile X pre-mutation carriers have normal intellect, but some can develop physical symptoms over time and are also more likely to develop social anxiety and depression.

Methylation of restriction sites that are routinely targeted in fragile X syndrome (FXS) diagnostics in blood have limited prognostic utility in dysexecutive impairments in Fragile X mental retardation1 gene (FMR1) premutation (PM) women and do not represent well the FMR1 activation ratio (AR) and deficient FMR1 protein (FMRP) levels in other tissues.


Scientists at Monash University (Victoria, Australia) compared 35 women who had the pre-mutation to 35 women who did not have this genetic change. The participants took tests of their brains’ executive functioning skills, such as inhibition and selective attention, and rated themselves on scales for depression and social anxiety. They also had blood tests to measure the amount of methylation in the Fragile X gene.

The CGG sizing and methylation analysis were performed on whole blood DNA. The CGG sizing was performed using the AmplideX FMR1 polymerase chain reaction (PCR) kit (Asuragen; Austin, TX, USA). PCR products were assessed via capillary electrophoresis on the 3,130 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA). Reverse transcription real-time PCR was used for the FMR1 messenger RNA (mRNA) analysis of peripheral blood mononuclear cell RNA on a ViiA 7 Real-Time PCR System (Life Technologies; Grand Island, NY, USA).

The investigators found that the women with the pre-mutation who had high methylation levels were more likely to have depression, social anxiety, and problems with executive functioning skills. In this group, worse scores on the executive function skills were correlated with having increased symptoms of anxiety and depression; this relationship was not seen in the women who did not have the pre-mutation.

Kim M. Cornish, PhD, the lead author of the study said, “These results are exciting, because it means we could use an easily accessible blood test to help diagnose people who have the pre-mutation genetic abnormality and identify who is more likely to have problems and begin early treatment. This finding could also help us better understand the Fragile X pre-mutation, as we can develop studies based on whether women are likely to develop these disorders.” The study was published on March 25, 2015, in the journal Neurology.

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Monash University
Applied Biosystems
Life Technologies