Study uncovers new Parkinson's gene
Researchers led by the Medical University of Vienna in Austria have identified a new gene called VPS35 that impacts Parkinson's disease. The findings, published in the American Journal of Human Genetics, show that this gene is mutated in individuals with Parkinson's disease; it is the sixth one to be linked to the neurological disorder and the third dominant gene.
'We have taken ... a meaningful step forward in Parkinson's disease research,' explains Alexander Zimprich from the Department of Clinical Neurology at the Medical University of Vienna. 'VPS35 is one of the three genes which cause late-onset Parkinson's, at an age of about 60 years,' he explains.
In 2004, Dr Zimprich and his team discovered another dominant gene called LRRk2, which is the culprit 'sporadic' Parkinson's - a form of Parkinson's disease.
The researchers evaluated 30 million deoxyribonucleic acid (DNA) components in this study. To kick-start the investigation, the team assessed a seven-member Austrian family who received care for the disease at the Neurology Clinic of the Linz General Hospital over the course of many years. They then sequenced the all protein-coding DNA regions from two affected family members using sequencing technology, a recent innovation. Experts call this process 'next-generation' parallel sequencing.
The analysis was quick, something that would have been impossible a few years ago. The team discovered more than 20,000 variants of the gene in each patient. Following a number of filtration processes and several exclusion steps, the researchers uncovered only one mutation in the VPS35 gene that could have triggered Parkinson's in all of the seven family members.
According to the researchers, the proportion of all cases of this disease caused by the VPS35 gene is 1.0%. Thanks to this finding, it is possible to 'analyse the metabolic pathways of Parkinson's at the molecular level better', Dr Zimprich explains. Scientists working to further elucidate what goes on with Parkinson's would get a huge boost from this; to date, they have not been able to find the cause for the brain cell deterioration that is characteristic of the disease.
What also piqued the researchers' interest was to determine whether VPS35 is also involved in Alzheimer's disease. According to them, genetic variations of the cargo protein SORL1 were discovered in a growing number of patients suffering from Alzheimer's.
'To what extent there is a possible connection in the aetiology of the two most common neurodegenerative diseases is a fascinating question, but one which cannot yet be answered,' Dr Zimprich says.
Parkinson's disease ranks second among neurodegenerative diseases, after Alzheimer's disease. Experts say that some 20,000 Austrians are battling this disorder; around 10% of people are genetically predisposed. Typical symptoms include general hypokinesia (decreased bodily movement) and a characteristic tremor. It occurs more frequently in men than in women, and it becomes more common with age.
'Families with several affected members present a rare and important opportunity to identify these dispositions,' Dr Zimprich concludes.
Experts from other Austrian and Germany-based research institutes contributed to this study.
Data Source Provider: American Journal of Human Genetics; Medical University of Vienna
Document Reference: Zimprich, A. et al. (2011) 'A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease'. AJHG, 89: 168-175. DOI: 10.1016/j.ajhq.2011.06.008.
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