Researchers believe they have discovered a new genetic mutation that causes Parkinson’s disease.
The international research effort was led by Mayo Clinic neuroscientists and revolved around the study of a large Swiss family with a history of Parkinson’s disease. The scientists used advanced DNA sequencing technology to discover the mutation.
The study is published in the American Journal of Human Genetics.
“This finding provides an exciting new direction for Parkinson’s disease research,” said co-author Zbigniew Wszolek, M.D., a Mayo Clinic neuroscientist.
“Every new gene we discover for Parkinson’s disease opens up new ways to understand this complex disease, as well as potential ways of clinically managing it.”
The team found that mutations in VPS35, a protein responsible for recycling other proteins within cells, caused Parkinson’s disease in the Swiss family.
Mutated VPS35 may impair the ability of a cell to recycle proteins as needed, which could lead to the kind of errant buildup of protein seen in some Parkinson’s disease brains and in other diseases like Alzheimer’s disease, said co-author Owen Ross, Ph.D.
“In fact, expression of this gene has been shown to be reduced in Alzheimer’s disease, and faulty recycling of proteins within cells has been linked to other neurodegenerative diseases,” he said.
So far, mutations in six genes have been linked to familial forms of Parkinson’s disease, with many mutations identified as a direct result of the Mayo Clinic’s collaborative research efforts.
Investigators used a new genetic sequencing technique to find the VPS35 mutation, according to Ross. They used “exome” sequencing to look for shared variations in a pair of first cousins within a large Swiss family affected by Parkinson’s disease.
Collectively, exons, which provide the genetic blueprint used in the production of proteins, make up only 1 percent of the entire genome and so it is much easier to look for novel variations, causing changes in the protein sequence, that would represent possible disease-causing mutations, he said.
“Cousins only share about 10 percent of their genome, whereas parents and children or siblings share much more. This narrowed the field of novel variations for us,” said Wszolek, with VPS35 emerging as the latest Parkinson’s disease gene.
“There is much more we need to know about this gene,” Ross said. “Although it appears to be a rare cause of Parkinson’s disease, it seems to be very important from a mechanistic viewpoint for this disease and possibly other neurodegenerative disorders.”
Source: Mayo Clinic