A blood test may shed new light on Fragile X syndrome related disorders in women, according to a new study published in the March 25, 2015, online issue of Neurology®, the medical journal of the American Academy of Neurology. Fragile X is the most common inherited form of intellectual disability and the most frequent genetic cause of autism.
Fragile X, which is caused by a mutation in a single gene on the X chromosome, affects about 1 in 4,000 men and 1 in 6,000 women. Even more common are Fragile X carriers of a lesser change in the Fragile X gene called a premutation, occurring in 1 in 450 men and 1 in 150 women. Fragile X premutation carriers have normal intellect, but some can develop physical symptoms over time. They are also more likely to develop social anxiety and depression.
In the study, researchers compared 35 women who had the premutation 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. Methylation adds methyl groups to some of the DNA, which inactivates that part of the X chromosome. Methylation is one type of so-called epigenetic changes, alterations in genes during the lifetime that affect their expression.
The researchers found that the women with the premutation 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 premutation.
“These results are exciting, because it means we could use an easily accessible blood test to help diagnose people who have the premutation genetic abnormality and identify who is more likely to have problems and begin early treatment,” said study author Kim M. Cornish, PhD, of Monash University in Victoria, Australia. “This finding could also help us better understand the Fragile X premutation, as we can develop studies based on whether women are likely to develop these disorders.”
Fragile X-associated Disorders
The term Fragile X-associated Disorders (FXD) refers to a family of conditions all caused by changes in the same gene. The gene’s scientific name is “FMR1,” but it is commonly referred to as “the Fragile X gene.” At this time we know of three distinct Fragile X-associated Disorders, but research is ongoing to evaluate other, perhaps more subtle effects of changes in the Fragile X gene that may have implications for a person’s health.
Fragile X syndrome (FXS)
The most common inherited cause of intellectual disabilities, fragile X syndrome occurs in both males and females, though females generally have less severe symptoms. FXS can cause developmental and language delays, learning impairment, and behavioral and mental health issues. Individuals with FXS have a form of the Fragile X gene called a “full mutation.”
The study was supported by the Australian Research Council, Monash University, National Fragile X Foundation, Australian Postgraduate Award, Victorian Government, Australian National Health and Medical Research Council, Murdoch Children’s Research Institute, and Royal Children’s Hospital Foundation.
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The Three Fragile X-associated Disorders
Fragile X Syndrome
Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and the most common known genetic cause of autism or autism spectrum disorders. Symptoms of FXS include a range from learning disabilities to more severe cognitive or intellectual disabilities that were previously referred to as “mental retardation.” Delays in speech and language development are common, as are a variety of physical and behavioral characteristics. FXS is caused by a “full mutation” of the FMR1 Gene.
Fragile X-associated Tremor/Ataxia Syndrome
Fragile X-associated tremor/ataxia Syndrome (FXTAS) is a condition that causes balance, tremor and memory problems in some older male (and less commonly, female) “carriers” of the FMR1 gene. FXTAS is caused by a “premutation” of the FMR1 Gene.
Fragile X-associated Primary Ovarian Insufficiency
Fragile X-associated primary ovarian insufficiency (FXPOI) is characterized by decreased ovarian function, which can lead to infertility and early menopause in some female “carriers” of the FMR1 gene. FXPOI is caused by a premutation of the FMR1 Gene.
Fragile X-associated Disorders (FXD) can be passed on by carriers of the FMR1 gene mutation who have no apparent signs of an FXD. In some families a number of individuals may be affected, while in other families a diagnosed individual may be the only known family member to exhibit symptoms. Also, in some families, only carriers are identified and there are no apparently affected family members.
American Academy of Neurology