Autosomal dominant Parkinson's disease in a large German pedigree.

Parkinson¢s disease (PD) is a common disablingneurodegenerative disorder characterized bybradykinesia, rest tremor, rigidity, and posturalinstability with a prevalence of 2% in elderlypersons (1). Although the causative mechanismsare poorly understood for the classical form of PD,a genetic contribution to its etiology has unambig-uously been demonstrated. To date, at least eightgenes have been identified in families with inheritedparkinsonism, either with an autosomal recessivemode of inheritance [Parkin⁄PARK2 (2), PINK1⁄-PARK6 (3), DJ-1⁄PARK7 (4), ATP13A2⁄PARK9(5), PLA2G6⁄PARK14 (6), and FBXO7⁄PARK15(7)] or dominant transmission [SNCA⁄PARK1 (8)and LRRK2⁄PARK8 (9, 10)]. Moreover, severalgenes were shown to influence the susceptibility toor the age of onset of PD although the results arepartially inconsistent, for example, as for poly-morphisms in the apolipoprotein E gene (11, 12).Although parkinsonism is the clinical hallmarkof all of these inherited forms, there is evidence formarked intrafamilial phenotypic variability includ-ing cognitive and psychiatric disturbances, dysto-nia, or isolated tremor in at least a subset ofpedigrees. In some cases, there is also phenotypicoverlap with a subtype of hereditary fronto-temporal lobar degeneration combined withparkinsonism, caused by mutations in the