Disease causing mutation found in French-Canadians

October 01, 2018

A team of Canadian scientists, including researchers at the Montreal Neurological Institute and Hospital (The Neuro) has discovered the first French-Canadian founder mutation gene linked to synucleinopathies, a group of neurodegenerative diseases that includes Parkinson's disease (PD), dementia with Lewy-Bodies (DLB) and multiple system atrophy (MSA).

The mutation, known as p.Trp378Gly, is in the GBA gene, one of the most prominent genes involved in PD. The most common GBA mutations create a small risk of developing synucleinopathies, but in combination with other mutations the risk can increase dramatically.

The study found that one per cent of French Canadians with synucleinopathies have the GBA mutation. This mutation is specific to French Canadians and was probably inherited from a single common ancestor.

People who inherit this gene mutation from one parent become carriers of the mutation and are at risk of developing synucleinopathies. Those who inherit this gene mutation in addition to another mutation in GBA from both parents will develop Gaucher's disease (GD). GD symptoms include enlargement of the spleen and liver, low red blood cell level, lung disease, arthritis, bone pain and fractures, but symptoms vary among patients.

"We don't know how frequent this mutation is in the general French-Canadian population, but it doesn't appear to be very common. We're going to test additional subjects so we can determine its exact frequency," says Dr. Ziv Gan-Or, a genetics researcher at The Neuro and the study's lead author. "This mutation causes Gaucher's disease, so it has clinical importance for couples who want to have children. They can request genetic screening for this specific gene mutation."

The study involved genetic examination of 891 control patients, 436 PD patients, and 189 REM-sleep Behaviour Disorder (RBD) patients whose condition has a strong link to synucleinopathies. All PD and RBD patients were of French Canadian ancestry. The results were published in the print version of the journal Clinical Genetics on Oct. 1, 2018.
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In addition to The Neuro, researchers contributing to the study were from McGill University, Université Laval, Department of Pharmacology and Therapeutics (Montreal), University of Toronto, Hôpital du Sacré-Cœur de Montréal, Centre Hospitalier Universitaire Sainte-Justine (Montreal), and the Mark Freedman and Judy Jacobs Program for Gaucher Disease, Sinai Health System (Toronto).

This work was financially supported by the Michael J. Fox Foundation for Parkinson's research, the Canadian Consortium on Neurodegeneration in Aging (CCNA) and the Canadian Glycomics Network (GlycoNet). This research was also undertaken thanks in part to funding from the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) program. The access to part of the participants for this research has been made possible thanks to the Quebec Parkinson's Network.

About The Montreal Neurological Institute and Hospital

The Montreal Neurological Institute and Hospital - The Neuro - is a world-leading destination for brain research and advanced patient care. Since its founding in 1934 by renowned neurosurgeon Dr. Wilder Penfield, The Neuro has grown to be the largest specialized neuroscience research and clinical centre in Canada, and one of the largest in the world. The seamless integration of research, patient care, and training of the world's top minds makes The Neuro uniquely positioned to have a significant impact on the understanding and treatment of nervous system disorders. In 2016, The Neuro became the first institute in the world to fully embrace the Open Science philosophy, creating the Tanenbaum Open Science Institute. The Montreal Neurological Institute is a McGill University research and teaching institute. The Montreal Neurological Hospital is part of the Neuroscience Mission of the McGill University Health Centre.

McGill University

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