Causative gene detection and its functional analysis for autosomal dominant Sagamihara Parkinsonism

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We detected a missense mutation in the LRRK2 gene in members of the Japanese family with autosomal dominant Parkingson's desease (PD) (Sagamihara family) on whose basis the PARK8 PD locus was originally defined. Thus, LRRK2 was concluded to be the gene responsible for PARK8. The mutation identified was located in the kinase domain and was identical to that reported in one of the PARK8-linked Caucasian families, suggesting that this mutation is essential for the pathogenesis. The unique pathological features of the Sagamihara family, characterized by pure nigral degeneration without Lewy bodies, provided us with a valuable oppotunity to elucidate the protein structure-pathogenesis relationship of the gene product of LRRK2.