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Genetik von Bewegungsstörungen

Genetics of movement disorders

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Zusammenfassung

In den letzten Jahren wurden zahlreiche genetische Ursachen für Bewegungsstörungen wie Parkinson-Syndrom, Dystonie, Restless-legs-Syndrom und essenzieller Tremor identifiziert. Dabei trugen methodische Weiterentwicklungen wie genomweite Assoziationsstudien (GWAS) und Sequenzierungen der neuen Generation („next generation sequencing“, NGS) zu einem exponentiellen Anstieg bei der Detektion genetischer Varianten bei. Obwohl monogene Formen selten sind, stellen sie ein einzigartiges Modell dar, die Erkrankung nicht nur in ihrer manifesten Form zu studieren, sondern auch mutationstragende Risikopersonen in der präsymptomatischen Phase longitudinal zu beobachten. Die funktionelle Charakterisierung genetisch bedingter Veränderungen in Zell- und Tiermodellen kann weitere Hinweise zur Pathophysiologie geben. Sie bieten damit einen wichtigen Grundstein für die Ursachenforschung und Entwicklung neuer Therapieoptionen. In dieser Übersicht werden bekannte genetische Formen mit dem entsprechenden Phänotyp sowie genetische Risikovarianten für Bewegungsstörungen kurz vorgestellt und Erkenntnisse zur Funktion der beteiligten Proteine zusammengefasst.

Summary

A number of genetic causes of movement disorders including Parkinson disease, dystonia, restless legs syndrome or essential tremor have been elucidated in recent years. This process was accelerated by novel technologies including genome-wide association studies (GWAS) and next generation sequencing (NGS). Although monogenic forms are overall rare, they provide a unique opportunity to investigate mutation carriers who are still in the presymptomatic phase. As these subjects present individuals at risk to develop the disease, they have been included in longitudinal studies to unravel disease mechanisms and elucidate novel therapeutic targets. In addition, cell culture and animal studies have been performed to functionally characterize proteins mutated in different movement disorders to provide further insight into disturbed cellular pathways. In this article, we summarize known monogenic forms and the associated phenotype as well as genetic risk factors and review the function of relevant genes and proteins.

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  1. Institut für Neurogenetik, Universität zu Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Deutschland

    K. Lohmann

  2. Abteilung für Neurodegenerative Erkrankungen und Hertie Institut für Klinische Hirnforschung, Universität Tübingen, Tübingen, Deutschland

    K. Brockmann

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  1. K. Lohmann
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  2. K. Brockmann
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Correspondence to K. Lohmann.

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Lohmann, K., Brockmann, K. Genetik von Bewegungsstörungen. Nervenarzt 84, 143–150 (2013). https://doi.org/10.1007/s00115-012-3638-y

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  • DOI: https://doi.org/10.1007/s00115-012-3638-y

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