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Fehlende Erblichkeit bei genetisch komplexen Erkrankungen

Bedeutung für die Epilepsiegenetik

Missing heritability in complex genetic diseases

Importance for the genetics of epilepsy

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Zusammenfassung

Genetische Faktoren spielen bei vielen Epilepsiesyndromen eine Rolle. Obwohl bezüglich monogener Formen der Epilepsie bereits große Fortschritte in der Identifikation der zugrunde liegenden Gene gemacht wurden, stellen gerade die häufigen Epilepsiesyndrome, deren Vererbungsmodus komplex ist, eine Herausforderung dar. Eine besondere Schwierigkeit besteht darin, große phänotypisch einheitliche Kollektive zu generieren. Zwar gelingt dies bei anderen Erkrankungen z. T. leichter, es bleibt aber auch bei diesen ein großer Teil der Erblichkeit oft unerklärt. Dies hat zu dem Begriff der „fehlenden Erblichkeit“ geführt. Im vorliegenden Beitrag werden mögliche Ursachen dieses Phänomens diskutiert. Weiterhin wird aufgezeigt, inwieweit die neuesten Entwicklungen bei den Genotypisierungstechnologien helfen können, diese Wissenslücke zu füllen. Darüber hinaus werden beispielhaft aktuelle Befunde im Bereich der Epilepsiegenetik dargestellt.

Abstract

Genetic factors play a role in many epilepsy syndromes. Much progress has been made in the identification of genes for monogenic epilepsies; however, gene identification in common epilepsy syndromes with complex inheritance remains challenging. In particular, the generation of large and phenotypically similar cohorts poses a difficulty. This can be more easily archived in various other diseases; however, even then a considerable amount of the heritability often remains unexplained and has led to the term missing heritability. In this article potential causes for this phenomenon will be discussed. It will also be shown how the newest developments in genotyping technology can help in unraveling this mystery. Furthermore, current findings in epilepsy genetics are presented in an exemplary manner.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. B.A. Neubauer und K.M. Klein geben an, dass kein Interessenkonflikt besteht. Das vorliegende Manuskript enthält keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Abteilung Kinderneurologie, Sozialpädiatrie und Epileptologie, Universitäts-Kinderklinik Gießen und Marburg, Standort Gießen, Feulgenstr. 12, 35835, Gießen, Deutschland

    B.A. Neubauer

  2. Epilepsiezentrum Hessen, Klinik für Neurologie, Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg, Philipps-Universität, Marburg, Deutschland

    K.M. Klein

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  1. B.A. Neubauer
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  2. K.M. Klein
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Correspondence to B.A. Neubauer.

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Neubauer, B., Klein, K. Fehlende Erblichkeit bei genetisch komplexen Erkrankungen. Z. Epileptol. 27, 82–92 (2014). https://doi.org/10.1007/s10309-013-0351-1

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  • DOI: https://doi.org/10.1007/s10309-013-0351-1

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