Maturity Onset Diabetes of the Young (MODY): Eine monogene Form der pankreatischen β-Zell-Dysfunktion

Zusammenfassung

Der Begriff „Maturity-Onset Diabetes of the Young“ (MODY) subsumiert unterschiedliche Syndrome des früh auftretenden Typ-2-Diabetes mit autosomal dominanter monogenetischer Ätiologie. Mittlerweile spricht man von bis zu zehn verschiedenen Genen, die ursächlich sind. Eine Klassifizierung der mit MODY-assoziierten Gene weist auf, dass es sich in erster Linie um Transkriptionsfaktoren des genregulatorischen Netzwerks der pankreatischen β-Zelle handelt. Dementsprechend kann der MODY als eine monogene Form der β-Zell-Dysfunktion mit direkter Genotyp- / Phänotyp-Korrelation durch Mutationen in spezifischen Genen für die einzelnen MODY Subtypen betrachtet werden. Da allerdings jedes Individuum ein einmaliges, individuelles Genom, das durch die Summe aller genetischen Variationen und Veränderungen bestimmt wird, aufweist, macht erst dieses sogenannte „genetische Setting“ die Suszeptibilität aus, die für die Ausprägung, aber auch Progression eines bestimmten Syndroms verantwortlich ist. Anders ausgedrückt stellt das genetische Setting quasi den Rahmen dar, in dem der individuelle Lebensstil ausgestaltet werden kann, ohne dass sich ein Phänotyp manifestiert. In dieser Übersicht wird weniger auf die einzelnen Gene eingegangen, als vielmehr die Einsicht vermittelt, dass MODY eine monogene Form der β-Zell-Dysfunktion ist, die man als eine genetische Suszeptibilität mit eindeutiger unausweichlicher Prognose betrachten kann. Hieraus resultiert, dass die Progression der β-Zell Dekompensation bis zu einem gewissen Ausmaß durch Änderung des Lebensstils, wenn nicht verhindert, so doch wenigstens verzögert werden kann. Deshalb gestattet die molekulare Analyse der Kandidatengene Aufschluss über das individuelle genetische Setting eines Probanden zu geben und damit einen Hinweis auf das Risiko bzw. die genetische Prädisposition für die Entwicklung einer monogenen Form der β-Zell-Dysfunktion.

Abstract

The term “Maturity-Onset Diabetes of the Young” (MODY) summarizes different syndromes of early onset type-2-diabetes with autosomal dominant inherited monogenetic etiology. Meanwhile up to ten genes have been identified to be causative. A classification of MODY associated genes re­vealed them mainly as transcription factors of the gene regulatory network necessary for pan­creatic β-cell function and development. There­fore MODY can be seen as monogenic form of β-cell dysfunction with direct genotype / phenotype correlation caused by mutations in specific genes for the various MODY subtypes. However, every individual has a unique individual genome de­fined by the sum of all genetic variations and variants that makes up the personal “genetic setting” accounting for the susceptibility being respon­sible for the development and progression of a syndrome. In other words, the genetic setting is sort of framework in which the individual lifestyle can be designed without a phenotype manifested. This overview is less addressed to discuss the different genes, but rather conveys the idea that MODY is a monogenic form of β-cell dysfunction, which can be regarded as a genetic susceptibility, with clearly inevitable prognosis. The result is that the progressions of β-cell decompensation, to some extent by changes in lifestyle cannot be prevented, but will at least be delayed. Therefore the molecular analyses of candidate genes allows to sheds light on the individual genetic setting of a subject and thus give an indication of the risk or the genetic predisposition for the development of a monogenic form of β-cell dysfunction.

Schlüsselwörter

MODY - Diabetes - monogener Diabetes - β-Zell-Dysfunktion

Key words

MODY - diabetes - monogenetic diabetes - β-cell dysfunction

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