[The long journey to the discovery of PARK2]

It was acknowledged long ago that Parkinson's disease (PD) occur rarely in familial aggregations. Willige and Mjönes noted no difference between the clinical features of the familial form and those of sporadic PD. Research into this aspect remained at a standstill for several decades thereafter. The resurgence of research into familial parkinsonism was the discovery by Japanese neurologists of autosomal recessive form of PD. In 1965, at Nagoya University, our research group examined familial cases of early onset parkinsonism. Clinical features included autosomal recessive inheritance, symptomatic alleviation after sleep, hyperreflexia, foot dystonia, good response to medication, and benign course without dementia. The clinical study of four families of the disease (EPDF) was published in Neurology in 1973. Subsequently, I kept on with my study of EPDF at Hiroshima University. Pathological study by our group in 1993 revealed neuronal loss in the substantia nigra without Lewy bodies. Based on these clinical and pathological evidences, EPDF was successfully defined as a distinct disease entity. Screening for the EPDF gene was started in 1994 in collaboration with Juntendo University. With the discovery of parkin gene in 1998, EPDF was designated as PARK2. Of our 16 families examined for gene analysis, fifteen proved to be PARK2, and the resting one, PARK6.