Parkinson's disease gene discovery

US researchers have found mutations in a gene that may lead to Parkinson's disease in families with a history of the neurodegenerative disorder. They hope the findings will lead to an improved understanding of the poorly understood disorder, and the development of new treatments.

Parkinson's disease is a disorder of the nervous system whereby patients, from an around 50 years old, see progressive worsening of symptoms such as tremors, slow movement, stiffness, balance problems and coordination. In the UK each year 10,000 patients are diagnosed - 25 per cent of these cases have a family history of the disorder.

The gene in question, GIGYF2, came to light five years ago in studies into insulin, the hormone that controls blood sugar levels. The link to Parkinson's was only drawn when it was mapped to a region of the genome that a 2002 paper had strongly associated with the disorder, without distinguishing any specific genes.

With this association in mind, the most recent study, published in the American Journal of Human Genetics, looked for GIGYF2 gene mutations in 249 French and Italian patients who had Parkinson's and at least one first-degree relative (parent, child or sibling) with the disease. The gene was also studied in 200 healthy controls.

They found seven different forms of the mutation in 12 different patients - five per cent of those in the study. Eight of these patients had at least one parent with Parkinson's, one had both parents affected, and three had one sibling affected. Where possible, affected relatives were also tested and were universally found to carry the same mutation. No mutations were seen in the healthy controls.

'Our data provides strong support for GIGYF2 as a PARK11 gene with a causal role in familial Parkinson's disease. The next step is to zero in on this gene to learn more about its involvement in triggering Parkinson's. It will also be important to evaluate additional and larger families with Parkinson's and these genetic mutations, as well as the frequency of GIGYF2 mutations in patients with the more common, idiopathic form of the disease', said senior author Robert J. Smith, M.D., an endocrinologist from the Hallett Center for Diabetes and Endocrinology at Rhode Island Hospital.

GIGYF2 is one of many genes to be linked to Parkinson's disease but one of only two known to commonly contribute to the disorder (the Parkin gene being the other).