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Molekulare Grundlagen der autosomal-rezessiven primären Mikrozephalie

Molecular basis of autosomal recessive primary microcephaly

Zusammenfassung

Die primäre autosomal-rezessive Mikrozephalie (MCPH) ist eine genetisch sehr heterogene Erkrankung, die klinisch definiert wird durch das Vorliegen einer kongenitalen, nicht progressiven Mikrozephalie, einer mentalen Retardierung variablen Ausmaßes bei weitgehend normaler Körpergröße und das Fehlen von zusätzlichen Fehlbildungen und weiteren neurologischen Befunden. Bislang konnten Mutationen in 14 verschiedenen Genen identifiziert werden, deren Produkte auf zellulärer Ebene insbesondere bei Vorgängen der Zellteilung, der Zellzyklusregulierung und bei der Aktivierung von DNA-Reparaturmechanismen nach DNA-Schädigungen eine wichtige Rolle spielen. Darüber hinaus sind auch syndromale Formen der Mikrozephalie bekannt, zu denen u. a. das Seckel-Syndrom sowie der mikrozephale osteodysplastische primordiale Kleinwuchs Typ II (MOPD II) zählen.

Abstract

Autosomal recessive primary microcephaly (MCPH) is a genetically very heterogeneous disorder, mainly characterized by severe microcephaly at birth, mental retardation of variable extent in the absence of any additional significant neurological findings, malformations, or growth anomalies. So far, 14 different genes have been identified, which on a cellular level play an important role during cell division processes, regulation of the cell cycle, and in DNA damage responses. Furthermore, microcephaly may occur as part of a syndrome such as Seckel syndrome or microcephalic osteodysplastic primordial dwarfism type II (MOPD II).

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Danksagung

Die Autoren danken allen Patienten sowie deren Angehörigen für ihre Mitarbeit. Forschungsarbeiten zu diesem Thema wurden durch das BMBF im Rahmen des E-RARE Netzwerkes EuroMicro (Förderkennzeichen 01GM1404) gefördert.

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Correspondence to Bernd Wollnik.

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Für die Autoren G. Yigit, N. Rosin und B. Wollnik besteht kein Interessenkonflikt.

Alle beschriebenen Untersuchungen am Menschen wurden mit Zustimmung der zuständigen Ethik-Kommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Alle Patienten, die über Bildmaterial oder anderweitige Angaben innerhalb des Manuskripts zu identifizieren sind, haben hierzu ihre schriftliche Einwilligung gegeben.

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Yigit, G., Rosin, N. & Wollnik, B. Molekulare Grundlagen der autosomal-rezessiven primären Mikrozephalie. medgen 27, 345–350 (2015). https://doi.org/10.1007/s11825-015-0068-9

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Schlüsselwörter

  • Primäre Mikrozephalie
  • MCPH
  • Seckel-Syndrom
  • Mikrozephaler osteodysplastischer Kleinwuchs Typ II (MOPD II)

Keywords

  • Primary microcephaly
  • MCPH
  • Seckel syndrome
  • Microcephalic primordial dwarfism type II (MOPD II)