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Genetische Risikovarianten beim Parkinson-Syndrom und anderen Bewegungsstörungen

Genetic risk variants in Parkinson’s disease and other movement disorders

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Zusammenfassung

Bewegungsstörungen sind häufig komplex-genetische Erkrankungen, bei denen genetische Risikofaktoren eine große Rolle spielen. Während z. B. beim Parkinson-Syndrom (PS) monogene Ursachen für nur 2–5 % der Erkrankungen verantwortlich sind und dies meist junge Patienten mit einem frühen Erkrankungsbeginn (<40. Lebensjahr) betrifft, scheinen häufige genetische Varianten bei der Mehrheit der Patienten das Risiko zur Entstehung der Erkrankung zu erhöhen. Bisher wurden 24 solcher Risikovarianten gefunden. Beim Restless-legs-Syndrom (RLS) sind noch keine monogenen Formen, aber sechs verschiedene Risikogenorte bekannt. Weniger gut aufgeklärt sind Risikogene für essenziellen Tremor und Dystonien, wofür nur fünf bzw. zwei verschiedene Kandidaten beschrieben wurden, deren Rolle aber (noch) nicht in unabhängigen Studien untermauert werden konnte. Im Rahmen dieses Artikels wird ein Überblick über diese Gene, deren Funktion und mögliche ursachenspezifische therapeutische Interventionen gegeben.

Abstract

Movement disorders are often genetically complex with genetic risk factors playing a major role. For example, monogenic causes of Parkinson’s disease (PD) can be found in only 2–5% of patients who often have an early onset (<40 years). In the majority of patients, common genetic variants seem to contribute to the disease risk. To date, 24 genetic risk factors have been identified. For restless legs syndrome (RLS), six different risk variants have been reported but no monogenic cause is known yet. For the genetic risk factors of essential tremor and dystonia, which are less well studied, only five and two candidate variants, respectively, have been described but their roles still require independent confirmation. In this review, we provide an overview on the involved genes, their function, and discuss possible, disease mechanism-driven therapies.

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Förderung

K. Brockmann erhält Forschungsförderung vom Bundesministerium für Bildung und Forschung (BMBF; 01EK1606D) von der Michel J Fox Stiftung und der Universität Tübingen. K. Lohmann erhält Forschungsförderung von der Deutschen Forschungsgemeinschaft (FOR2488) und dem Bundesministerium für Bildung und Forschung (DYSTRACT, 01GM1514B).

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Authors and Affiliations

  1. Zentrum für Neurologie, Abteilung Neurodegeneration, Hertie-Institut für klinische Hirnforschung, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Universität Tübingen, Hoppe Seyler Straße 3, 72076, Tübingen, Deutschland

    K. Brockmann

  2. Institut für Neurogenetik, Universität zu Lübeck, Lübeck, Deutschland

    K. Lohmann

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Correspondence to K. Brockmann.

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K. Brockmann und K. Lohmann geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Brockmann, K., Lohmann, K. Genetische Risikovarianten beim Parkinson-Syndrom und anderen Bewegungsstörungen. Nervenarzt 88, 713–719 (2017). https://doi.org/10.1007/s00115-017-0348-5

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