Genetic discovery for hereditary spastic ataxia—rare disease in Newfoundland

September 6, 2012

Researchers from the Guy Rouleau Laboratory affiliated with the CHUM Research Centre and the CHU–Sainte-Justine Research Centre have discovered the genetic cause of a rare disease reported only in patients originating from Newfoundland: hereditary spastic ataxia (HSA).

This condition is characterized by lower-limb spasticity (or stiffness) and ataxia (lack of coordination), the latter leading to speech and , and eye movement abnormalities. The disease is not deadly, but people start developing gait problems between 10 to 20 years of age, walk with a cane in their 30s, and in the most severe cases, are wheel-chair bound in their 50s. It has been shown that HSA is transmitted from the affected parent to the child in a dominant fashion, which means there is a 50% chance of the child having the mutation.

History of a discovery: collaboration between the University of Montreal and Memorial University

Researchers and clinicians from Memorial University (St. John's, Newfoundland) contacted Dr. Rouleau, who is also a professor of medicine at the University of Montreal, over a decade ago to investigate the genetics behind this disorder occurring in three large Newfoundland families. Dr. Inge Meijer, a former in the Rouleau Laboratory, discovered that these families were ancestrally related, and in 2002, identified the locus (DNA region) containing the mutation causing HSA.

A few years later, Cynthia Bourassa, lead author of the study, took over Meijer's project. "I reexamined some unresolved details using newer and more advanced methods," explains Bourassa, who is a master's student in the Faculty of Medicine at the University of Montreal. She then teamed up with Dr. Nancy Merner, who after obtaining her Ph.D. at Memorial University moved to Montreal to further her career in . "It is an honour to be a part of this study and impact the lives of my fellow Newfoundlanders. I knew coming into the Rouleau Laboratory that the genetic factors of the HAS families had not yet been identified. In fact, I asked about them on my first day of work, shortly after which I teamed up with Cynthia and we found the gene."

Scientific explanation:

The gene harbouring the mutation is VAMP1, encoding the synaptobrevin protein. "Not only was the mutation present in all patients and absent from all population controls, but also, synaptobrevin is a key player in neurotransmitter release, which made sense at the functional level as well," says Bourassa. In fact, the authors believe that this mutation in the VAMP1 gene may affect neurotransmission in areas of the nervous system where the synaptobrevin protein is located, causing the unique symptoms of HSA. In other words, there are not enough messengers released, so nerves cannot function optimally.

"The discovery will benefit the families affected with this extremely debilitating disorder," says Dr. Rouleau. "A genetic diagnostic test can be developed, and genetic counseling can be provided to family members who are at risk of developing the disease or having children with the condition."

Identification of the VAMP1 mutation was made in the Guy Rouleau Laboratory in collaboration with investigators from Newfoundland, Nova Scotia, and Ontario. Funding was provided by the Canadian Institutes for Health Research, the Canada Research Chair, and the Jeanne-et-J.-Louis-Levesque Chair for the Genetics of Brain Diseases.

Explore further: De novo mutations provide new genetic clues for schizophrenia

More information: "VAMP1 Mutation Causes Dominant Hereditary Spastic Ataxia in Newfoundland Families." Authors: Cynthia V. Bourassa, Inge A. Meijer, Nancy D. Merner, Kanwal K. Grewal, Mark G. Stefanelli, Kathleen Hodgkinson, Elizabeth J. Ives, William Pryse-Phillips, Mandar Jog, Kym Boycott, David A. Grimes, Sharan Goobie, Richard Leckey, Patrick A. Dion, Guy A. Rouleau. The American Journal of Human Genetics (2012), doi: 10.1016/j.ajhg.2012.07.018

Related Stories

De novo mutations provide new genetic clues for schizophrenia

July 10, 2011
De novo mutations – genetic errors that are present in patients but not in their parents – are more frequent in schizophrenic patients than in normal individuals, according to an international group of scientists ...

Molecular mechanisms offer hope for new pain treatments

August 4, 2011
By working with individuals suffering from a severe disorder that causes sensory neurons to degenerate, researchers at the University of Montreal Hospital and CHU Sainte-Justine Hospital have discovered how a specific genetic ...

Researchers find genetic cause for body tremors

August 2, 2012
Researchers at the University of Montreal and its affiliated CHU Sainte-Justine and CHUM hospitals have linked some cases of Essential Tremor (ET) to a specific genetic problem. ET is the most common movement disorder, becoming ...

A pill to prevent migraine? Discovery of migraine gene could put it on the horizon

June 1, 2011
The discovery of a gene for migraine holds great promise in the quest for new approaches -- possibly even a pill -- for preventing the disease, says a panel of experts presenting data at the annual scientific meeting of the ...

Recommended for you

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

Newly identified genetic marker may help detect high-risk flu patients

July 17, 2017
Researchers have discovered an inherited genetic variation that may help identify patients at elevated risk for severe, potentially fatal influenza infections. The scientists have also linked the gene variant to a mechanism ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.