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Identification of ataxia genes

Project details

Professor Henry Houlden
UCL Queen Square Institute of Neurology
Research area
Funding type
Project grant
Awarded in
April 2014
December 2018

Cerebellar ataxia is a progressive, degenerative condition that is usually caused by genetic defects, and inherited from one generation to the next. There is no known effective treatment or cure for this condition, which affects an estimated 50,000 people in the UK.

In this project, Professor Henry Houlden assessed patients and family members to identify hitherto unknown ataxia genes. This will aid future effective diagnosis, and inform the development of new treatments for this condition.

About spinocerebellar ataxia

Spinocerebellar ataxias are a group of hereditary movement disorders that are characterised by degenerative changes in the part of the brain related to the control of movement (cerebellum) and sometimes the spinal cord.

There are different types of spinocerebellar ataxia (SCA), which have different signs and symptoms but are characterised by problems with movement that tend to get worse over time. Signs and symptoms can onset anytime from childhood to late adulthood.

There is no cure for SCA. Some symptoms can be treated with medicine and therapy, and the best options will depend on the particular symptoms experienced, as well as the underlying genetics, where known.

For most people, symptoms get progressively worse, severely affecting their ability to walk and talk and to live independently.

Read more: About ataxia

Identifying ataxia genes

Cerebellar ataxia is usually caused by defective genes and inherited from one generation to the next. There have been a number of different ataxia genes identified but many patients are undiagnosed, or go years without knowing the exact type of ataxia.

Some ataxia genes are dominant - meaning that a single copy of the gene, inherited from either parent, results in development of the disease.

Some ataxias are recessive - meaning that two copies of the gene, one from each parent, are required for development of the disease. In these cases, people are often not aware that they carry the ataxia gene until they have children who begin to show signs of having the disorder.

Our funding contributed to a wider project in which Professor Houlden and team assembled 432 ataxia families in the UK that had no diagnosis. The team has so far performed genetic sequencing on 168 of these families. This has led to the identification of 34 rare ataxia gene defects.

One common and important group of ataxias have a later age at onset and can be difficult to differentiate from other neurodegenerative disorders. Late-onset ataxia is usually idiopathic - that is, it has no known cause. The team has identified a hitherto unknown mutation in the gene RFC1, underlying the familial form of a type of late-onset ataxia known as CANVAS (cerebellar ataxia, neuropathy, vestibular areflexia syndrome).


Spinocerebellar ataxia is a distressing degenerative condition, with limited treatment options.

Information about the specific genetic cause of an individual's disease is important because it helps to ensure accurate diagnosis, inform treatment strategy and provide prognostic information about the likely course of the disease. But whilst a number of disease genes have been identified for ataxia, around 40 per cent of individuals and families remain genetically undefined.

In this project, Professor Houlden has identified an important cause of ataxia - a mutation in the RFC1 gene - and has helped stimulate further research into this mutation. This gives insight into how the mutation affects normal function and gives rise to the symptoms associated with the disease.

This work was published in March 2019 in Nature Genetics.

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