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New Genetic Mutation Linked to Parkinson's

Using a new, cutting-edge technology for gene sequencing, researchers funded in part by the Parkinson’s Disease Foundation (PDF), have discovered a new gene called vesicular sorting protein complex 35 (VPS35) that is linked to Parkinson’s disease (PD) in people with familial PD.  The results appear in the July 14 issue of the American Journal of Human Genetics.

In recent years, researchers have identified about a dozen genes that either cause PD or increase the risk of developing the disease.  In general, the motor symptoms of PD begin at a young age in people who have mutations in genes that cause PD.  People with mutations in the newly discovered gene, however, were diagnosed with PD around the age of 50.

To search for a new PD gene, an international team of researchers led by Carles Vilariño-Güell, Ph.D., and Matthew J. Farrer, Ph.D., at the University of British Columbia, Vancouver, focused on a family from Switzerland in which 11 people in three generations were diagnosed with PD.  They compared the DNA of family members with PD to that of unaffected family members to search for differences that could explain why some developed PD and others did not.

In the past, this type of DNA analysis has been very difficult, requiring examination and DNA collection from large numbers of affected families. The University of British Columbia researchers instead used a new and efficient technique called whole exome sequencing, which focuses on small, but important, sentence-like sections of DNA.  These sections govern the production of proteins. Since mutated proteins are most often the cause of genetic diseases, they reasoned that mutations linked to inherited PD would be found here. 


  • In all 11 members of the Swiss family who had PD, the scientists identified a mutation in the VPS35 gene.
  • Among 190 additional families that had many cases of PD, the researchers found the same VPS35 mutation in eight members of three families from the United States, Tunisia, and Israel (Yemenite Jews).
  • The VPS35 mutation was found in one person with no family history of PD.
  • The researchers tested DNA samples from more than 3,000 healthy individuals from several countries and found no mutations in VPS35. 

What Does it Mean? 

Like most other genetic causes of PD, this newly identified genetic mutation is exceedingly rare, resulting in very few cases of PD.  However, these rare mutations have helped scientists generate key insights into the disease and a broad understanding of why people may develop PD. This new study is the first to implicate VPS35 in PD.  Consequently, these results will need to be replicated in other populations in order to confirm this finding and assess the frequency of this mutation.

Nevertheless, VPS35 is already known to play a role in disease.  The gene plays a central role in a neuron’s protein recycling center as part of the so-called retromer system. Breakdowns in the retromer pathway have already been linked to neurodegenerative diseases such as Alzheimer’s and Charcot-Marie-Tooth, the latter is a disease of the peripheral motor and sensory nerves. Therefore, a better understanding of how a VPS35 mutation causes cellular processes to go awry may help scientists unravel the causes of PD and other neurodegenerative diseases. 

Reference: Carles Vilariño-Güell, Christian Wider, Owen A. Ross, Justus C. Dachsel, Jennifer M. Kachergus, Sarah J. Lincoln, Alexandra I. Soto-Ortolaza, Stephanie A. Cobb, Greggory J. Wilhoite, Justin A. Bacon, Bahareh Behrouz, Heather L. Melrose, Emna Hentati, Andreas Puschmann, Daniel M. Evans, Elizabeth Conibear, Wyeth W. Wasserman, Jan O. Aasly, Pierre R. Burkhard, Ruth Djaldetti, Joseph Ghika, Faycal Hentati, Anna Krygowska-Wajs, Tim Lynch, Eldad Melamed, Alex Rajput, Ali H. Rajput, Alessandra Solida, Ruey-Meei Wu, Ryan J. Uitti, Zbigniew K. Wszolek, François Vingerhoets, Matthew J. Farrer. VPS35 Mutations in Parkinson Disease. The American Journal of Human Genetics - 15 July 2011 (Vol. 89, Issue 1, pp. 162-167). 

Source Date: Jul 15 2011