What is being tested?
The FMR1 gene contains the DNA code to produce a protein called FMRP. This protein is present in a variety of tissues but is especially important in the brain. FMRP is essential for proper brain development and seems to play a role in ensuring that the connections between nerve cells (known as synapses), develop and function properly.
How is it used?
FMR1 mutation testing is used to assess the FMR1 gene in a person. The FMR1 gene is carried on the X chromosome. Males have only one X chromosome (and one Y chromosome). Therefore they have only one copy of the FMR1 gene in each cell in their bodies. Women, have two X chromosomes, and therefore have two copies of the gene in each cell. In women one of the X chromosomes in each cell is randomly inactivated such that in any given cell only one of the two copies of FMR1 is active. This is important in how women can be less severely affected by mutations in the FMR1 gene.
The vast majority of Fragile X syndrome (>99%) is caused by an alteration (mutation) in the FMR1 gene where a DNA segment, known as the CGG triplet repeat, is expanded. Normally, this DNA segment has from 5 to about 54 of the CGG triplets. In people with Fragile X syndrome, however, the CGG triplet is repeated more than 200 times (known as a "full mutation"). The abnormally expanded CGG segment inactivates the FMR1 gene, which prevents the gene from producing a protein called fragile X mental retardation protein (FMRP). Loss of this protein leads to the signs and symptoms of Fragile X syndrome. Both boys and girls can be affected, but because boys have only one X chromosome in each cell, an FMR1 mutation will affect all their X chromosomes and they will be more severely affected. About 50 per cent of women with one copy of the full mutation will have some degree of learning problems that can range from mild to severe but most women are much less severely affected than men with a full mutation.
People with a medium-size repeat sequence of 55 – 200 repeats are said to have a premutation in the FMR1 gene. They will not have intellectual disability or Fragile X syndrome in childhood as enough FMRP protein is still produced. They are however, at risk of developing problems later in life. Both men and women with premutations are at risk of developing a neurodegenerative disorder after middle age with slowly worsening movement problems that may be misdiagnosed as Parkinson’s syndrome, with memory loss, reduced sensation in the lower limbs and behavioural changes (Fragile X associated tremor/ataxia syndrome, or FXTAS). Women with premutations also have a moderate risk of developing ovarian failure and going into menopause before the age of 40 (Fragile X associated primary ovarian insufficiency, or FXPOI).
When is it requested?
FMR1 gene testing is ordered in children when they have intellectual disability that is consistent with the possibility of Fragile X syndrome. In adults, FMR1 gene testing may be ordered when the person has progressive neurodegeneration with ataxia, memory loss and other features consistent with Fragile X tremor/ataxia syndrome. Women with premature ovarian failure may also be tested to see if they are premutation carriers. FMR1 gene testing may be recommended if you have a relative with an FMR1 mutation.
What does the result mean?
Because the FMR1 gene is on the X chromosome it has a special pattern of inheritance called X-linked and is only partly recessive since around 50 per cent of women do express the condition to some degree. The test results can show a short or normal repeat length, a medium or premutation repeat length or a long or full mutation repeat length. An important factor is how the gene behaves when it is passed down to children from either their mother or their father.
Is there anything else I should know?
Very rarely Fragile X syndrome can be caused by different types of mutations in the FMR1 gene in areas away from the CGG repeats. The usual tests for CGG repeat number will not detect these types of mutations.
It is not offered in every laboratory. In most cases, your blood will be sent to a reference laboratory for testing.
No, you inherit a copy of the gene from each of your parents and they will not change over time. However, repeats in the premutation range can increase to become a full mutation in the next generation.
FMR1 testing is covered by Medicare in people affected by intellectual disability, ataxia, neurodegeneration, or premature ovarian failure consistent with an FMR1 mutation or if the person has a relative with an FMR1 mutation.
Pathology Tests Explained (PTEx) is a not-for profit group managed by a consortium of Australasian medical and scientific organisations.
With up-to-date, evidence-based information about pathology tests it is a leading trusted sources for consumers.
Information is prepared and reviewed by practising pathologists and scientists and is entirely free of any commercial influence.