The mutation, located on a gene called VPS35, was identified using a novel technology called exome sequencing, which allowed scientists to reveal all gene mutations from an individual. Details of the study are published today in The American Journal of Human Genetics.
“We applied this technology to DNA samples from two cousins diagnosed with Parkinson’s disease. They are part of a Swiss family where eleven people have developed the disease,” says lead author Carles Vilariño-Güell, a post-doctoral research associate in UBC’s Dept. of Medical Genetics and a member of the Centre for Molecular Medicine & Therapeutics (CMMT).
“We found one previously unidentified mutation was present in all the individuals in this family who had developed Parkinson’s disease, but we did not see this mutation in any of the more than 3,000 healthy individuals whose DNA samples we studied,” says Vilariño-Güell.
He and senior author Matthew Farrer subsequently found the VPS35 mutation in eight more patients with Parkinson’s disease from three other families, and one patient with no family history of disease. The families originated in countries as geographically disparate as Tunisia and the United States.
“This conclusively proves that this mutation is the cause of disease in these patients,” says Vilariño-Güell.
Farrer, a professor in the Dept. of Medical Genetics and Canada Excellence Research Chair in Neurogenetics and Translational Neuroscience at UBC, says the identification of the VPS35 mutation provides new clues for understanding the pathological mechanisms that lead to Parkinson’s disease.
VPS35 is a critical component of a protein recycling system in neurons, called the retromer. Deficiencies in the retromer system have previously been linked to Alzheimer’s disease and other neurological conditions such as Charcot-Marie-Tooth.
“Our findings show, for the first time, that the retromer system is also an important mechanism for Parkinson’s – and perhaps other neurological disorders,” says Farrer, who’s also a senior scientist at CMMT and a member of the Brain Research Centre at UBC and Vancouver Coastal Health Research Institute.
Prior discoveries have identified mutations in five genes that predispose people to developing Parkinson’s.
“This new finding provides another piece of the Parkinson’s puzzle that will allow us to investigate what’s going on in the brains of people with Parkinson’s – and to work towards developing and testing novel therapies to halt, treat, and potentially cure this terrible disease,” says Farrer, who joined UBC from the Mayo Clinic in Jacksonville, Florida last year.
More than 100,000 Canadians, approximately one million Americans and more than 10 million people worldwide are affected by Parkinson’s disease. Symptoms include trembling in hands, arms, legs, and face, stiffness in the limbs and torso, as well as slow movement and poor balance and coordination. There is currently no cure and most treatments only tackle the symptoms.
Vilariño-Güell first presented the discovery in March at the International Alzheimer’s disease and Parkinson’s disease congress in Barcelona. He was awarded the Greenberg Family Award, which is given to talented young scientists with the intent of advancing their research into the diagnosis and treatment of Parkinson’s disease.
Researchers throughout the world are now checking their genetic samples based on Farrer and Vilariño-Güell’s findings as they pursue a deeper understanding of the biological processes triggered by the VPS35 mutation that result in the development of Parkinson’s disease.
The research was supported by the Michael J. Fox Foundation, the Parkinson’s Disease Foundation, and the Canada Excellence Research Chairs program.
The Brain Research Centre comprises more than 200 investigators with multidisciplinary expertise in neuroscience research ranging from the test tube, to the bedside, to industrial spin-offs. The centre is a partnership of UBC and VCH Research Institute. For more information, visit www.brain.ubc.ca.
The Centre for Molecular Medicine and Therapeutics is a synergistic group of scientists and researchers who share a strong sense of commitment to solve the many genetic questions surrounding human illness and well being. Affiliated with the University of British Columbia and the Child & Family Research Institute, CMMT conducts discovery research and translates that research into effective clinical and therapeutic strategies to promote health. For more information, visit www.cmmt.ubc.ca.
The UBC Faculty of Medicine provides innovative programs in the health and life sciences, teaching students at the undergraduate, graduate and postgraduate levels. Its faculty members received $303 million in research funds, 55 percent of UBC’s total research revenues, in 2009-10. For more information, visit www.med.ubc.ca
Vancouver Coastal Health Research Institute (VCHRI) is the research body of Vancouver Coastal Health Authority, which includes BC’s largest academic and teaching health sciences centres: VGH, UBC Hospital, and GF Strong Rehabilitation Centre. In academic partnership with the University of British Columbia, VCHRI brings innovation and discovery to patient care, advancing healthier lives in healthy communities across British Columbia, Canada, and beyond. www.vchri.ca.