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Genomik und Proteomik in der Erforschung neuromuskulärer Erkrankungen

Genomics and proteomics in the research of neuromuscular diseases

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Zusammenfassung

Neurologische Erkrankungen betreffen 3–5 % aller Kinder und nehmen bei Erwachsenen, insbesondere in der alternden Population Westeuropas, neben Herz‑/Kreislauf- und Tumorerkrankungen die häufigste Ursache für Morbidität und Mortalität ein. Neuromuskuläre Krankheitsbilder sind eine Untergruppe der neurologischen Erkrankungen und haben häufig eine genetische Ursache, was zu einer familiären Häufung führt. Trotz des enormen Fortschritts in der Analyse des Erbguts wie beispielsweise durch Sequenzanalysen der kodierenden Desoxyribonukleinsäureregionen oder der gesamten Desoxyribonukleinsäure bleibt die genetische Ursache bei ca. der Hälfte der Patienten, die an seltenen Formen neurologischer Erkrankungen leiden, ungeklärt. Gründe hierfür werden in diesem Artikel aufgeführt. Im Falle des Vorhandenseins von Therapiekonzepten kann dies unter Umständen einen Einfluss auf die frühzeitige und adäquate Behandlung der Patienten haben. Unter Betrachtung der neuromuskulären Erkrankungen als Paradigmen stellt dieser Artikel neben den Vorzügen des Einzugs der „Next-generation-sequencing“-Analyse-basierten DNA-Untersuchungen als eine Omics-Technologie („genomics“) zudem den Vorzug der Integration dieser mit Proteinanalysen („proteomics“) dar. Dabei wird ein besonderes Augenmerk auf die Kombination von Genomik und Proteomik in Sinne eines proteogenomischen Ansatzes bei der Diagnostik und Erforschung der Erkrankungen gelegt. In diesem Sinne wird im Rahmen dieses Artikels ein proteogenomischer Ansatz im Kontext eines multidisziplinären Projektes zur verbesserten Diagnostik und zukünftigen Therapie von Patienten mit neuromuskulären Erkrankungen vorgestellt; NME-GPS: Gen- und Protein-Signaturen als globales Positionsbestimmungssystem bei Patienten mit neuromuskulären Erkrankungen.

Abstract

Neurological diseases affect 3–5% of children and, apart from cardiovascular diseases and cancer, represent the most prominent cause of morbidity and mortality in adults and particularly in the aged population of western Europe. Neuromuscular disorders are a subgroup of neurological diseases and often have a genetic origin, which leads to familial clustering. Despite the enormous progress in the analysis of the genome, such as by sequence analysis of coding regions of deoxyribonucleic acid or even the entire deoxyribonucleic acid sequence, in approximately 50% of the patients suffering from rare forms of neurological diseases the genetic cause remains unsolved. The reasons for this limited detection rate are presented in this article. If a treatment concept is available, under certain conditions this can have an impact on the adequate and early treatment of these patients. Considering neuromuscular disorders as a paradigm, this article reports on the advantages of the inclusion of next generation sequencing analysis-based DNA investigations as an omics technology (genomics) and the advantage of the integration with protein analyses (proteomics). A special focus is on the combination of genomics and proteomics in the sense of a proteogenomic approach in the diagnostics and research of these diseases. Along this line, this article presents a proteogenomic approach in the context of a multidisciplinary project aiming towards improved diagnostic work-up and future treatment of patients with neuromuscular diseases; “NMD-GPS: gene and protein signatures as a global positioning system in patients suffering from neuromuscular diseases”.

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ERDF (European Regional Development Fund (ERDF)) PD Dr. rer. nat. Andreas Roos.

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  1. Abteilung für Neuropädiatrie, Universitätsmedizin Essen, Hufelandstrasse 55, 45147, Essen, Deutschland

    Andrea Gangfuß, Ulrike Schara-Schmidt &  Andreas Roos

  2. Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Kanada

    Andreas Roos

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  1. Andrea Gangfuß
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Gangfuß, A., Schara-Schmidt, U. & Roos, A. Genomik und Proteomik in der Erforschung neuromuskulärer Erkrankungen. Nervenarzt 93, 114–121 (2022). https://doi.org/10.1007/s00115-021-01201-1

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