Parkinson's Disease Due to Extra Genes (cont.)

Major New Finding on Genetics of Parkinson's Disease Zeroes In on Activity of Alpha Synuclein

Scientists investigating a rare familial form of early-onset Parkinson's disease have discovered that too much of a normal form of the a-synuclein gene may cause Parkinson's disease. The finding, reported in the October 31, 2003, issue of Science, shows that abnormal multiplication of the a-synuclein gene can cause the disease

The study provides major new clues into the process by which Parkinson's disease develops. Further, it suggests another way of looking at the consequences of abnormal protein deposition in a variety of neurological diseases, such as Alzheimer's disease.

The Science findings were reported by Andrew Singleton, Ph.D., and colleagues at the National Institute on Aging's (NIA) Laboratory of Neurogenetics, Matthew Farrer, Ph.D., of the Mayo Clinic, and Katrina Gwinn-Hardy, M.D., of the National Institute of Neurological Disorders and Stroke (NINDS). The team also included scientists from the National Human Genome Research Institute (NHGRI) and Georgetown University Medical Center, Washington, DC.

Until very recently, researchers focused on possible environmental factors as the culprit in Parkinson's disease. However, in 1996, mutations in the a-synuclein gene were identified in a few large families in whom the disease was unusually common. Since then, mutations in several other genes have also been linked to familial forms of Parkinson's disease.

In this new study, investigators analyzed blood samples from another affected family, the "Iowa kindred," in which many relatives developed Parkinson's disease or related neurological diseases. The family, followed by this team of researchers for many years, presented a puzzle to scientists because the genetic analyses of some family members initially showed no a-synuclein mutation. The scientists thought perhaps an entirely different genetic mutation might account for Parkinson's disease in this family and had even given this other gene a name, PARK4.

Not satisfied that they had the answer, scientists on the team decided to look again at genetic samples from the family, conducting additional analyses of the entire genome, including chromosome 4, the chromosome on which the a-synuclein gene is located. In individuals in this family affected by Parkinson's disease, instead of the usual two copies of the a-synuclein gene in the chromosome 4 pair, the researchers found four copies of the a-synuclein gene. This multiplication of the a-synuclein gene (an abnormal triplication of three genes on one chromosome 4 and the normal one copy on the other chromosome 4) results in the individual's having too much synuclein. This protein buildup is believed to cause the Parkinson's disease symptoms.