Summary

FMR1 gene testing is most commonly ordered in children when they have an intellectual disability that is consistent with the possibility of Fragile X syndrome. It may also be used in the investigation of the elderly with a late-onset progressive neurodegeneration disorder when they have poor muscle control -known as ataxia - memory loss and other features consistent with Fragile X tremor/ataxia syndrome. Women with premature ovarian failure – early menopause - may also be tested to see if they are premutation carriers. FMR1 gene testing may also be recommended if you have a relative with an FMR1 mutation.

Why get 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.
The FMR1 gene is carried on the X chromosome. Males who have only one X chromosome – and one Y chromosome– have only one copy of the FMR1 gene. Women, who have two X chromosomes, have two copies of the gene. In women, one of the X chromosomes is randomly inactivated such that in any given cell only one of the two copies of FMR1 is active. This is important in understanding how women can be less severely affected by mutations in the FMR1 gene.

Full mutation in the FMR1 gene
The vast majority of Fragile X syndrome – more than 99 per cent – is caused by an alteration – a mutation – in the FMR1 gene where a DNA segment, known as the CGG triplet repeat, is expanded. 
This is where the DNA pattern of the chemical letters, CGG, is repeated over and over again. Different people have different numbers of these CGG repeats, but most people have between 5 and 54 of the CGG triplets. People with Fragile X syndrome have many more, usually more than 200.  This is known as a full mutation.

The abnormally expanded CGG segment turns off the FMR1 gene and prevents it from producing a protein called fragile X mental retardation protein or 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 occur in 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 difficulties that can range from mild to severe but in general, women are much less severely affected than men with a full mutation.

Premutation in the FMR1 gene
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 because enough FMRP protein is still being produced but they are 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 – memory loss, reduced sensation in the lower limbs and behavioural changes. This is known as 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.

Having the test

Sample 
Blood 
Any preparation?
None

Your results

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 about 50 per cent of women 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. 
Implications for inheritance
An important factor is how the gene behaves when it is passed down to children from the mother or the father.
Short or normal repeats are stable and the length does not change when passed on to children.

Any more to know?

The Medicare schedule permits testing when a person is affected by intellectual disability, ataxia, neurodegeneration, or premature ovarian failure consistent with an FMR1 mutation or the person has a relative with a FMR1 mutation.

FMR1 gene testing is not offered in every laboratory. In most cases, your blood will be sent to a reference laboratory for testing.

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.

More information

Pathology and diagnostic imaging reports can be added to your My Health Record. You and your healthcare provider can now access your results whenever and wherever needed.
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