TORONTO - Several British Columbia families with high rates of a form of early onset dementia or ALS or both have played a key role in helping researchers pinpoint a common genetic cause of the two diseases.
American and Canadian scientists reported Wednesday that they have discovered a genetic fault that is linked to a high likelihood of developing one and sometimes both of the debilitating neurological conditions.
The mutation is not the only cause of the diseases, but appears to account for a larger percentage of cases than any of the causative mutations identified to date.
The findings were published in the journal Neuron.
The mutation was found through study of several families badly afflicted by frontotemporal dementia — sometimes called Pick's disease — and ALS, which is also know as Lou Gehrig's disease.
One particularly affected family with members in British Columbia, San Francisco and Florida even brought together the research team, which includes scientists from the Mayo Clinic's Jacksonville, Fla., campus, the University of California, San Francisco and the University of British Columbia.
Dr. Ian Mackenzie, a neuropathologist at UBC and Vancouver General Hospital, said DNA samples from these families, as well as brain tissues taken in autopsies of members who have died, were key in identifying the location of the mutation.
"It seems to be the predominant and maybe the only genetic mechanism that explains these large families with both ALS and FTD," Mackenzie said in an interview from Germany. He noted, though, that the mutation is also a cause of a percentage of cases of what is called sporadic ALS and FTD — cases where there is no family history of the disease.
Frontotemporal dementia or FTD is the second most common cause of early onset neurodegenerative dementia; Alzheimer's disease is the first. Its hallmarks are personality, behavioural and language changes, caused by loss of grey matter in the frontal and temporal lobes of the brain.
ALS destroys motor neuron cells, resulting in the progressive loss of the ability to walk, speak and eventually swallow and breathe.
It's been previously noted that the diseases appear to be linked. Up to half of ALS patients develop symptoms of FTD and about an equal proportion of FTD patients show symptoms of ALS-like motor dysfunction. And in families with high rates of diseases, both are seen.
"What those families were telling us is that there's also a common genetic basis in some cases at least," MacKenzie said.
The problem is a DNA sequence that repeats hundreds and sometimes thousands of times, an abnormal occurrence on that gene at that spot. That buildup of excessive DNA coding seems to kill affected cells, Mackenzie said.
Another research group, which looked at family clusters in Finland, reported similar findings in the same issue of Neuron.
Knowing this genetic source of the disease will help scientists try to develop better diagnostic and predictive tests, Mackenzie suggested. Those could help people in afflicted families assess their personal risk of developing one of the diseases, or help them decide whether or not to have children.
As well, it could help in the search for drugs to prevent the onset of these diseases or mitigate the damage they cause.