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

我们在日本常染色体显性遗传性帕金森病(PD)家族(相模原家系)的成员中发现了LRRK2基因的错义突变，Park8 PD基因座最初是基于该突变定义的。因此，LRRK2被认为是Park8的致病基因。发现的突变位于蛋白激酶结构域，与Park8连锁的高加索家族中报道的突变完全相同，提示该突变在发病机制中起重要作用。Sagamihara家族独特的病理特征，以单纯黑质变性为特征，没有路易小体，为我们阐明LRRK2基因产物的蛋白质结构与发病关系提供了有价值的机会。

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.