Following on from our ’year of hope’ appeal last month an international team of researchers, including two funded by the MND Association, have identified mutations in the Matrin 3 (MATR3) gene as a cause of the rare inherited form of MND.
Medical Research Council (MRC)/ MND Association Lady Edith Wolfson Clinical Research Fellow Dr Pietro Fratta was involved in the research, which was published on 30 March 2014 in the prestigious journal Nature Neuroscience.
Inherited MND is a rare form of MND (5-10% of total MND cases) and the MATR3 gene is the latest to be identified. This rare form of MND is characterised by a family history of MND.
New gene, new gene
When a new gene is first identified this creates a great deal of ‘buzz’ amongst the MND research community, often generating more questions than answers:
- How common is this inherited MND gene?
- How does this gene cause MND?
This is the starting point for MATR3. Unfortunately, we just don’t know the answers to these questions at the moment. Hopefully MND researchers will now use the discovery of MATR3 to find the answers to these questions and further our understanding of this gene.
How did they find MATR3?
Identifying MATR3 was no easy task. The international team of researchers identified a family, with European ancestry, where several family members had been diagnosed with MND. By using a technique called exome sequencing they were able to screen the entire DNA of the family (known as a genome) to look for specific gene changes.
Exome sequencing is used to quickly copy the entire DNA of an individual, allowing researchers to look for changes in specific genes. This technique only focuses on the exomes (the coding region of the DNA that contains the information needed for making new proteins).
By studying this part of the DNA the researchers were able to look for changes in the proteins without having to sieve through the non-coding housekeeping DNA. In doing so, the researchers identified a new mutation in the MATR3 gene.
To check the mutation was not found in healthy controls, the researchers screened the control databases of over 27,000 genomes. After reviewing the databases the researchers concluded that the MATR3 mutation was the likely cause of inherited MND in the family.
More evidence for RNA
After identifying MATR3 as a cause of inherited MND, the researchers went on to explore how the gene causes MND on a cellular level. By investigating cells from individuals with the MATR3 mutation, the researchers identified higher amounts of the MATR3 protein than normal.
The MATR3 protein is commonly found in the nucleus or ‘control centre’ of the cell and is involved in the processing of RNA (the cell’s copy of DNA that is responsible for making new proteins). RNA processing has been previously associated with other inherited MND mutations (eg TARDBP and FUS). The MATR3 mutation also affects this process, adding more evidence to the role of abnormal RNA processing in MND.
What this means for people living with MND
Mutations in the MATR3 gene have been identified as a rare cause of inherited MND. Due to this research being the first to identify this gene we do not fully understand what this protein does or how common it is.
This research has also provided more evidence to support the role of abnormal RNA processing in MND – furthering our understanding of the disease and the processes involved.
Dr Fratta recently presented his research at our spring conference in East Sussex on Saturday 29 March. Commenting on this research, Dr Fratta said: “This finding is extremely important and adds evidence for the role of RNA metabolism defects in MND. Although MATR3 mutations appear to be rare, they will allow us to tackle the issue of RNA metabolism defects in MND from another angle and further our knowledge in this mechanism of disease”
Dr Brian Dickie, our Director of Research said: “This research has opened up a new avenue for MND researchers to explore. Identifying the MATR3 gene is the first step, now we need to find out how common it is and, importantly, how this mutation causes MND.
“The international team of researchers have already begun to answer the latter, highlighting RNA processing, and the cell’s ability to make new proteins, as an important area of future MND research.”
2014 is fast becoming a year of hope for MND research thanks to this recent MND gene discovery, with MND researchers around the world working together towards a world free from MND. Find out how you can help here.