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Molekulare Karyotypisierung in der klinischen Diagnostik

Molecular karyotyping in clinical diagnosis

Zusammenfassung

Molekulare Karyotypisierung bezeichnet die genomweite Analyse bezüglich genetischer Kopienzahlveränderungen mit Hilfe von Arrays, welche das Genom mehr oder weniger dicht mit molekularen Markern abdecken. Die Hauptanwendung in der klinischen Diagnostik liegt derzeit bei der Analyse von Patienten mit geistiger Behinderung und multiplen Anomalien unbekannter Ursache. Bei ihnen lassen sich nach Ausschluss von konventionell-zytogenetisch sichtbaren Aberrationen, kryptischen subtelomerischen Aberrationen und klinisch gut erkennbaren, häufigen Mikrodeletionssyndromen in rund 10% der Fälle mittels molekularer Karyotypisierung chromosomale Mikroaberrationen nachweisen. Hierdurch konnten in den letzten Jahren zahlreiche neue Mikrodeletions- und -duplikationssyndrome charakterisiert werden, jedoch wurde auch ersichtlich, dass die Interpretation von Einzelbefunden aufgrund der großen Anzahl an genomischen Kopienzahlpolymorphismen nicht trivial ist.

Abstract

The term “molecular karyotyping” refers to the genome-wide analysis of copy number variations using arrays that cover the genome with genomic markers with varying density. Currently the main application is the investigation of patients with otherwise unexplained mental retardation and multiple congenital anomalies. Studies of such patients who remained without etiological diagnosis after conventional karyotyping, subtelomeric screening, and targeted molecular–cytogenetic studies for well-known microdeletion syndromes revealed chromosomal microaberrations in about 10% of cases and allowed the delineation of several new microdeletion and microduplication syndromes. Nevertheless, because of the large number of copy number polymorphisms, interpretation of unique findings needs thorough consideration.

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Rauch, A. Molekulare Karyotypisierung in der klinischen Diagnostik. medgen 20, 386–394 (2008). https://doi.org/10.1007/s11825-008-0135-6

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Schlüsselwörter

  • Molekulare Karyotypisierung
  • Array-CGH
  • SNP-Array
  • Mentale Retardierung
  • Mikrodeletionssyndrome

Keywords

  • Molecular karyotyping
  • Array CGH
  • SNP array
  • Mental retardation
  • Microdeletion syndromes