New motor neurone disease gene found

Thursday September 22 2011

The Daily Telegraph reported that there would be a blood test for inherited motor neurone disease ‘in months’. The newspaper reported that a cross-university team has “pinpointed the genetic fault that is behind more cases of inherited MND than any other”.

The news report is based on research by an international collaboration of many institutions that found a repeated sequence of DNA in about a third of all people with inherited MND. The researchers knew that a region on chromosome 9 was associated with the disease but were able to use new techniques to analyse large sections of DNA to find the particular sequence underlying the effect. They found that there were repeated sequences of DNA in a gene called C9ORF72.

The researchers estimate that combining a test for this repeated DNA sequence with other gene mutations known to be associated with the condition could detect about 90% of those with familial MND in the Finnish cohort they looked at. Testing for this gene will help to identify people with a family history of MND who are at risk of developing the condition, but as yet it is not clear when this test would be ready for UK families. It will also focus research on how the repeated sequence affects the working of the C9ORF72 gene. This may lead to greater understanding of the disease itself.

The research found this genetic link in people who had a family history of MND, but 90%-95% of people who develop MND have no family history of it. However, approximately 21% of non-familial cases they tested had the mutation, suggesting that further research is needed to see what other genes may increase  risk of the disease.

Where did the story come from?

The study was carried out by researchers from a large number of international research institutions including the National Institutes of Health, Bethesda, US; Cardiff University; University College London and University of Manchester. The study was funded by the National Institutes of Health, the National Institute on Aging and National Institute of Neurological Disorders and Stroke. The study was published in the peer-reviewed journal, Neuron .

This research was covered well by BBC News and The Daily Telegraph . The Telegraph did imply that this research was only done by British researchers when in fact there were 34 research groups involved and the lead researchers were from Bethesda in the US, with most samples coming from Finland.

What kind of research was this?

This was a genetics study that looked for particular genetic sequences associated with this type of motor neurone disease.

This condition is characterised by progressive paralysis and life expectancy is typically two to three years from symptom onset. It is the third most common neurodegenerative disease in the Western world. Approximately 5% of cases are familial, meaning that the person had a relative or relatives who also had the condition, but the remaining patients are classified as having ‘sporadic’ disease as the cases appear to occur randomly without a close family relative having the condition.

Researchers have previously looked at the genetic make-up of people with a family history of MND and a number of genes have been found to be associated with the condition. These past studies pointed to a broad region on chromosome 9 being particularly associated with the disease. A previous Finnish study found that this region was implicated in around half of familial cases and around a quarter of sporadic cases.

What did the research involve?

In the present study the researchers took DNA samples from a Welsh family where MND ran in the family and from a Dutch family. They focused on the region on chromosome 9 and used new sequencing technology to analyse large sections of DNA from members of each family, looking for a specific DNA sequence associated with the disease. The two families had a history of MND with frontotemporal dementia. Frontotemporal dementia (FTD) is a condition thought to be related to MND and some people with MND also have FTD although it is possible to have FTD without any symptoms of MND.

For each family researchers had a detailed family tree that showed which people had gone on to develop MND and people who had remained free of the disease. Some of the family members had MND only and others had FTD only. Some had MND with FTD. Researchers sequenced samples from one person with MND only, one person with FTD and one person with MND and FTD.

Once they had identified a particular sequence they were able to look at how often this sequence occurred in a much larger set of samples. They used samples from a Finnish cohort but also looked at DNA samples from people who had familial MND from other cohorts from North America,  Germany, Italy and also control DNA samples from individuals from a variety of countries.

What were the basic results?

The researchers said that they had previously found that the chromosome 9 region they looked at covered three genes called MOBKL2b, IFNK and C9ORF72. When they sequenced all of the DNA they found that there was a particular repeating sequence in the C9ORF72 gene.

They found that in a Finnish population the repeated sequence was found in 46% of people with familial MND and 21.1% of people with sporadic MND  They found that if they tested people for this sequence or a mutation that affects another gene called SOD1, then 87% of familial MND cases in Finland are explained by these genetic causes.

When they looked at samples from people with familial MND in the European cohorts (those with a wider European ancestry), a third had repeats of this sequence.

How did the researchers interpret the results?

The researchers said that the repeated sequence is the most common genetic cause of MND identified to date and is more than twice as common as mutations in the SOD1 gene as a cause of familial MND. It is more than three times as common as the combination of other genes that have been implicated.


This was important research that found a repeated sequence was associated with cases of motor neurone disease that runs in families, and is more common than other gene mutations that had previously been found.

However, although this sequence repeat was associated with MND and was common, not all people with MND had it.

This is a single gene defect and so it is likely that people who have a family history of MND will be offered testing for this sequence repeat and the other gene mutations that have been demonstrated to have an association with MND. As such it is an important advance for these families, but it is not clear when such a blood test would be available to UK families with a family history of this disease.

It remains possible that other, as yet undiscovered, gene variants may also contribute to the condition and the underlying defects for the majority of people who develop MND without having a family history is still unknown.

Analysis by Bazian
Edited by NHS Choices