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Chromosomale Ursachen der geistigen Behinderung

Chromosomal causes of mental retardation

Zusammenfassung

Aneuploidien und Aneusomien stellen die häufigste bekannte Ursache mentaler Retardierung (MR) dar. Neben zahlenmäßigen Aberrationen ist eine Reihe von Mikrodeletionssyndromen klinisch und molekular gut definiert. Mit der Entwicklung von Verfahren zur systematischen, genomweiten Analyse auf Kopienzahlveränderungen mittels Array- oder Matrix-CGH („comparative genomic hybridization“) sowie Oligonukleotidmikroarrays konnten jüngst mehrere weitere Mikrodeletions- und Mikroduplikationssyndrome aufgedeckt werden. Neben rekurrenten Bruchpunkten zwischen repetitiven Sequenzen werden auch zahlreiche „private“ Aberrationen mit variablen Bruchpunkten gesehen, die meist andere Entstehungsmechanismen haben. Neben klinisch charakteristischen Syndromen sind mehrere Aberrationen durch extrem variable Expressivität und Penetranz gekennzeichnet, weshalb neben de novo aufgetretenen auch über scheinbar gesunde Eltern vererbte Aberrationen pathogenetisch relevant sein können. Das phänotypische Spektrum reicht von MR mit und ohne kongenitale Fehlbildungen bis hin zu psychiatrischen Erkrankungen, wobei Mikroduplikationen meist mit einer milderen phänotypischen Ausprägung als die entsprechenden Deletionen einhergehen.

Abstract

Aneuploidies and aneusomies are the most frequent known causes of mental retardation (MR). Besides numerical aberrations, a number of microdeletion syndromes are well known, both clinically and at the molecular level. With the advent of methods for systematic genome-wide analysis of copy number variation such as array comparative genomic hybridization and oligonucleotide microarrays, various novel microdeletion and microduplication syndromes have been uncovered. In addition to recurrent breakpoints mediated by low-copy repeats, numerous “private” aberrations with variable breakpoints due to several other molecular mechanisms have been observed. Some aberrations result in clinically recognizable syndromes, while many exhibit broad clinical variability and penetrance. In consequence, not only de novo aberrations are to be considered, but some pathogenic relevant aberrations can be inherited through apparently healthy parents. The phenotypic spectrum reaches from MR with and without congenital anomalies to psychiatric disorders. Microduplications are usually associated with milder phenotypes than are reciprocal deletions.

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Danksagung

Besonderer Dank gilt den Patienten und deren Familien für die Teilnahme an unserer Forschung sowie die Bereitschaft zur Publikation ihrer Fotos.

Die Arbeit der Autoren zu dieser Thematik wurde und wird von der Deutschen Forschungsgemeinschaft (DFG) und über das MRNET-Projekt vom Bundesministerium für Bildung und Forschung (BMBF) gefördert.

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Reis, A., Rauch, A. Chromosomale Ursachen der geistigen Behinderung. medgen 21, 237–245 (2009). https://doi.org/10.1007/s11825-009-0166-7

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Schlüsselwörter

  • Mentale Retardierung
  • Mikrodeletionssyndrome
  • Mikroduplikationssyndrome
  • Molekulare Karyotypisierung
  • MRNET (German Mental Retardation Network)

Keywords

  • Mental retardation
  • Microdeletion syndromes
  • Microduplication syndromes
  • Molecular karyotyping
  • MRNET (German Mental Retardation Network)