Major cause of MND discovered on chromosome 9

An international research team, co-funded by the Motor Neurone Disease Association of England, Wales & NI (MND Association), has identified a new gene on chromosome 9 that appears to cause nearly 40% of cases of the inherited form of motor neurone disease (MND). This is the most common cause of the disease found to date and the discovery could lead to tests for families who have a history of MND.

The investigators studied a large group of Finnish patients and a family from Wales who have lost relatives to early onset MND and the neurodegenerative disease frontotemporal dementia (FTD and also known as Pick’s disease). The team comprising of scientists from six different countries, including scientists from Cardiff, Manchester and University College London, discovered that the Welsh family and the Finnish patients share a genetic mistake on chromosome 9.

Chromosome 9 has been of interest to international researchers for a number of years. Previous work had identified an area that appeared to be significantly associated with both MND and FTD but up until now researchers could not pinpoint the gene on chromosome 9 which is involved in the disease.

In this new work, funded by the MND Association, the Medical Research Council (MRC) and the ALS Association, the genetic mistake was identified in the Finnish and Welsh DNA samples as a repeated six letter DNA sequence. Unaffected people carry up to 20 DNA repeats in a gene called C9orf72 whereas the patient samples carried hundreds of repeats. This is known as a ‘repeat expansion’.

The genetic variant had been difficult to identify with the researchers locating  it in the most unlikely of places – in the stretches of DNA that do not provide instructions for manufacturing proteins (proteins are the ‘building blocks’ of cells), otherwise known as non-coding DNA.

The exact role of this repeat expansion in the C9orf72 gene is currently unknown but it probably disrupts multiple mechanisms in motor neurones leading to their failure and death.

Although this gene was first identified in the Finnish and Welsh samples, further research has shown that it also occurs in familial (inherited) MND patients from North America, Germany and Italy and appears to account for the disease in 38% of patients with the inherited form of MND.

Dr Brian Dickie, Director of Research Development, at the MND  Association, said: “Discoveries in genetics are driving the ever-increasing momentum of motor neuron disease research. Chromosome 9 has been a prime suspect in motor neurone disease for some time but pinning down the precise genetic factor involved had proved elusive. The discovery of this rogue gene has the potential to significantly advance our understanding of motor neurone disease, helping scientists to home in on the pivotal cellular changes underlying all forms of the disease.”

Association-funded researcher Dr Huw Morris, based at the MRC Centre for Neuropsychiatric Genetics, Cardiff University and the Royal Gwent Hospital, who worked as a member of the international scientific team is now working on a test for those with a family history of the disease that could be rolled out by early 2012.

He said: “This work is the culmination of many years work by doctors and scientists studying this condition and it is due in large part to the courage and tenacity of many patients facing MND, particularly the Welsh family and the Finnish cohort.  Although this work is the end of our long hunt for this gene, it is the beginning of our search for therapies based on this discovery that can stop this brutal disease in its tracks.”

We recommend that anyone who has a family history of MND and who would like to know more about the new test discusses this with their doctor/specialist nurse.