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Parkinson's disease gene link strengthened

26 January 2006
By BioNews
Appeared in BioNews 343

US researchers have found that many cases of Parkinson's disease (PD) in certain ethnic groups could be triggered by a single faulty gene. In two separate studies, the scientists discovered that some patients with an Ashkenazi Jewish or Arabic background have a mutated version of the LRRK2 gene. The findings, published in the New England Journal of Medicine, should help shed light on the biological basis of the disease, and could lead to new treatments.

People with PD are affected by tremors, stiff muscles and slow movements, caused by a gradual loss of nerve cells in an area of the brain controlling movement. It is not known what triggers this loss, but PD is not normally inherited. However, the illness does occasionally run in families, where the symptoms often appear at a younger age than in non-inherited cases. Researchers think that there are around ten different types of inherited PD, each involving a different gene.

Last year, scientists based in the Netherlands, the US and the UK identified the LRRK2 gene, which makes a protein called dardarin - named after the Basque word for 'tremor'. They found that as well as causing around five per cent of inherited cases of PD, it is also implicated in 1-2 per cent of 'sporadic' cases. In the latest research, teams based at the Albert Einstein College of Medicine in New York, and the INSERM institute in Paris, France, investigated the incidence of the most common LRRK2 gene mutation in US Ashkenazi Jews and North African Arabs.

The US researchers studied DNA samples from 120 unrelated Ashkenazi Jews with PD, and compared it with DNA from 317 unaffected people. They found that the LRRK2 mutation was present in around 18 per cent of the patients, and 1.3 per cent of the controls. Their results suggest that the mutation - which changes a single amino acid 'building block' in the dardarin protein chain - increases the estimated risk of the disease by about 15-fold in this population.

The French team studied DNA from 104 affected North African people, along with samples from 151 healthy, unrelated controls. They found that amongst North African Arab patients, 37 per cent had the LRRK2 mutation, compared to just two per cent of the controls. The US team conclude that both studies together point to a Middle Eastern origin for the genetic change.

US team leader Susan Bressman says that 'genetics are going to be a lot more important in Parkinsons than people have appreciated'. She is in favour of offering tests, accompanied by counselling to those at risk of the disease because of their ethnic background. However, Ephrat Levy-Lahad, of the Shaare Zedek Medical Centre in Jerusalem, disagrees. 'Before we put tests into clinical practice, we have to have something to tell the patient who is asking 'now what do I do?', he told the Washington Post newspaper.

Genetic Link to Parkinson's Disease Is Detected in 2 Ethnic Groups
LA Times |  26 January 2006
Genetic Link to Parkinson's Is Discovered
The Washington Post |  26 January 2006
Researchers identify gene mutation as major cause of Parkinson's in Ashkenazi Jewish patients
EurekAalert |  26 January 2006
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