Many people with ataxia do not have a specific genetic diagnosis and the cause of their ataxia is unknown. Two papers have been published which have identified a genetic mutation that might be a common cause of late-onset ataxia (ataxia where the start of symptoms occurs relatively later in life). This type of ataxia has been named late-onset spinocerebellar ataxia 27B (SCA27B).
The newly discovered mutation, which is thought to cause SCA27B, is found in a gene called fibroblast growth factor 14 (FGF14). In the human genome there are many different repeated sequences.  The number of repeats varies between people, and this does not normally cause a problem. However, sometimes if someone has a too high number of repeats in a certain gene, this can cause a person to develop a condition, such as ataxia. This type of mutation is called a repeat expansion. Repeat expansions in different genes cause other types of ataxia; for example, Friedreich’s ataxia and Spinocerebellar ataxias (SCAs) 1, 2, 3, 6 and 7. In the two studies, researchers found that some people with ataxia of a unknown cause had a high number of repeats of the GAA sequence in a section of their FGF14 gene.
In one study, researchers identified 128 people with ataxia who had equal to or greater than 250 GAA repeats in their FGF14 gene. They initially identified the mutation in several members of 3 French Canadian families. They then tested for the mutation in a larger number of people with ataxia from different countries. They found that out of the 345 people with ataxia they tested, 61% French Canadian participants, 18% German participants, 15% Australian participants, and 10% South Asian Indian participants had equal to or greater than 250 GAA repeats. This number of repeats was only found in less than 2% of control participants who did not have ataxia.
Nearly half of the people with the mutation had episodes of ataxia lasting from minutes to days when their ataxia first started. The average age these episodes started was 55 years, but this ranged from 30 to 87 years. The average age the progressive ataxia started was 59 years (range 30 to 88 years). Around half the people with the mutation had involuntary, rapid, and repetitive eye movements (nystagmus).
Another study, which included participants from Australia and Germany, also identified 28 people with ataxia who had more than 250 GAA repeats in their FGF14 gene (14% people tested). Several of the participants with ataxia had more than 335 GAA repeats, while none of the controls did. This suggests that if a person has more than 335 GAA repeats this will cause ataxia, while if the number of repeats is between 250-335, it is likely but not certain that someone will develop ataxia. Â The researchers saw that people with the mutation had a slowly progressing ataxia, with some people having other symptoms such as inner ear balance problems (vestibular dysfunction) and overactive body reflexes (hyperreflexia).
Both studies show that the FGF14 mutation could be a common cause of late-onset ataxia. The discovery of this genetic mutation may lead to more diagnoses for people with ataxia of unknown cause.
The test for the FGF14 mutation is not yet widely available. However, if your neurologist contacts researcher Dr David Pellerin, they can provide more information about genetic testing as part of their research project.
Contact details:
Dr David Pellerin and Professor Henry Houlden
Institute of Neurology, Queen Square, London WC1N 3BG
david.pellerin.21@ucl.ac.uk | david.pellerin2@mcgill.ca
The research papers can be found here and here. A description of SCA27B aimed at researchers and neurologists can also be found here.
