September 1997

A Gene for Parkinson Disease

Author Affiliations

From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md.

Arch Neurol. 1997;54(9):1156-1157. doi:10.1001/archneur.1997.00550210084017

Until recently, the possibility that genetic factors contributed significantly to the pathogenesis of Parkinson disease (PD) was accorded relatively short shrift. Few patients with obviously familial PD are seen in common practice, and families with parkinsonism often present with rather atypical features. The discovery that the neurotoxin N-methyltetrahydropyridine (MPTP) rapidly induces an illness similar to sporadic PD added fuel to those arguing that environmental factors must be largely responsible. But more recently, this view has begun to shift because no generally plausible environmental factors emerged and data favoring a genetic component began to mount.1 Now it is clear that the cause of PD may on occasion be purely genetic and involve autosomal dominant as well as various other inheritance patterns. Moreover, it has become increasingly apparent that even in sporadic cases, the disease most likely reflects some combination of genetic susceptibility and environmental insult. In such instances, the genetic component presumably acts by increasing the vulnerability of dopamine-containing neurons in the nigrostriatal system to injury by 1 or more common, possibly by themselves relatively innocuous, environmental factors. This view has now been substantially reinforced and our ability to understand the pathogenesis of PD dramatically advanced by the recent identification of a gene responsible for PD in 4 unrelated families.2