Genetik der Parkinson-Krankheit: Übersicht und praktische Hinweise zur genetischen Diagnostik

In addition to the nine well-defined monogenic forms of Parkinson's disease, there are numerous known genetic risk and protective variants that modulate the risk of Parkinson's disease. Among the monogenic forms, three (PARK1/PARK4, PARK8, PARK17) follow an autosomal dominant mode of inheritance, whereas six are recessively inherited (PARK2, PARK6, PARK7, PARK9, PARK14, PARK15). Six forms have clinical characteristics very similar to those of idiopathic Parkinson's disease (PARK1/PARK4, PARK2, PARK6, PARK7, PARK8, PARK17). Among the latter forms, late-onset PARK8 with mutations in the LRRK2 gene and early-onset PARK2 caused by mutations in the Parkin gene are by far the most common. Both the monogenic and the idiopathic forms of Parkinson's disease share common pathophysiological mechanisms involving oxidative modification, impaired protein degradation and mitochondrial dysfunction. Therefore, monogenic forms of Parkinson's disease can serve as human model diseases for the idiopathic forms.