New Parkinson disease gene identified

Jul 22, 2011

A team of researchers at the University Department of Neurology of the Medical University of Vienna has succeeded in identifying a gene that is mutated in individuals with Parkinson disease. The research team leader Alexander Zimprich said: "We have taken here a meaningful step forward in Parkinson’s disease research."

The newly discovered gene is known as VPS35, the sixth one which has been associated with Parkinson disease and the third dominant gene. "VPS35 is 1 of the 3 genes which cause late-onset Parkinson’s, at an age of about 60 years," explains Zimprich. Another dominant Parkinson disease gene had already been discovered by Zimprich’s team at the MedUni Vienna in 2004: the LRRk2 gene. This dominant gene causes a form of Parkinson disease similar to sporadic Parkinson disease.

The origin of the present research effort was an Austrian family with 7 affected members who had been under the care of the Neurology Clinic at the Linz General Hospital for many years. All protein-coding DNA regions from 2 affected family members were completely sequenced, aided by a sequencing technology that has only become available recently—next generation parallel sequencing.

Using this new technology, the scientists were able to analyze more than 30 million DNA components in just a few days. Such a comprehensive analysis of the whole genome in such a short time would have been unthinkable just a few years ago. More than 20,000 variants of the gene were found in each of the patients. After numerous filtration processes and various exclusion steps, there was finally only 1 mutation in the VPS35 gene which could be responsible for the disease in the members of this family (VPS35-Asp620Asn). The researchers estimate the proportion of all cases of Parkinson disease caused by this gene to be 1.0%. Indeed, Zimprich is of the opinion that we can "analyze the metabolic pathways of Parkinson’s at the molecular level better" because of this discovery. This would be of great value to researchers of this disease.

Other institutes in Austria and the Helmholtz Centre for Genetics in Germany also participated in this study under the direction of Asst Prof Dr Alexander Zimprich.

A certain cargo protein (SORL1) in particular aroused the interest of the research group: certain genetic variations of this same protein were found a few years ago in increased numbers in Alzheimer disease patients. “To what extent there is a possible connection in the etiology of the 2 most common neurodegenerative diseases is a fascinating question, but one which cannot yet be answered,“ said Zimprich.

Incidentally, a Canadian research group succeeded at the same time in identifying the same mutation in a large Swiss family. Both studies can be read in the current issue of American Journal of Human Genetics, the professional journal of the American Society of Human Genetics.

Source: News Release
Medical University of Vienna
July 20, 2011