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Molekulargenetische Diagnostik von Imprintingerkrankungen

Relevanz von Multilocusmethylierungsdefekten

Molecular diagnosis of imprinting disorders

Relevance of multilocus methylation defects


Bei allen derzeit bekannten Imprintingerkrankungen wurde über eine Assoziation mit molekularen Veränderungen an krankheitsspezifischen chromosomalen Loci berichtet. Die locusspezifische Zuordnung einiger dieser Krankheitsbilder wird erschwert durch den Nachweis so genannter Multilocusmethylierungsdefekte (MLMD): Dabei besteht nicht nur an krankheitsspezifischen geprägten Genorten eine aberrante Methylierung, sondern auch an anderen Loci. Klinisch zeigt sich mehrheitlich die Symptomatik nur einer Imprintingerkrankung, in einzelnen Fällen überlappen sich jedoch verschiedene Krankheitsbilder. Umgekehrt wurden auch Fälle mit gleichartigem MLMD-Muster, aber unterschiedlichen Krankheitsbildern beschrieben. Zur Abklärung von MLMD sollten daher Testverfahren eingesetzt werden, die auf Methylierungsveränderungen an verschiedenen geprägten Loci ausgerichtet sind. Aber auch bei der MLMD-Testung ist eine eindeutige Unterscheidung des zugrunde liegenden Mutationstyps als Basis für eine gezielte genetische Beratung erforderlich.


All currently known imprinting disorders (ID) have been associated with molecular alterations at disease-specific chromosomal loci. Locus-specific association of some of these disorders has been complicated by the identification of so-called multilocus methylation defects (MLMD). In addition to aberrant methylation at disease-specific loci, MLMD also affects other loci. Clinically, the majority of patients show symptoms of a single ID, but some overlapping phenotypes have been described. Furthermore, cases of patients with the same MLMD pattern but different clinical symptoms have also been reported. Molecular tests aimed at identifying MLMD should therefore be directed at various imprinted loci. To enable comprehensive genetic counseling, clear differentiation of the type of mutation underlying the ID is also a necessary component of MLMD testing.

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Die Autoren sind Mitglieder des vom Bundesministerium für Bildung und Forschung geförderten nationalen Netzwerks „Imprinting Diseases“ (Förderkennzeichen: 01GM0884).


Der korrespondierende Autor gibt für sich und seine Koautoren an, dass kein Interessenkonflikt besteht.

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Correspondence to T. Eggermann.

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Eggermann, T., Begemann, M., Soellner, L. et al. Molekulargenetische Diagnostik von Imprintingerkrankungen. medgen 25, 5–14 (2013).

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  • Genomisches Imprinting
  • DNA-Methylierung
  • Multilocussequenztypisierung
  • Angelman-Syndrom
  • Prader-Willi-Syndrom


  • Genomic imprinting
  • DNA methylation
  • Multilocus sequence typing
  • Angelman syndrome
  • Prader-Willi syndrome