medizinische genetik

, Volume 26, Issue 2, pp 246–254 | Cite as

Exomsequenzierung zur Identifizierung von Krankheitsgenen für seltene Syndrome

Erfahrungen aus Hamburg, Deutschland
  • F. Kortüm
  • H. Abdollahpour
  • M. Alawi
  • G.C. Korenke
  • E. Seemanova
  • S. Tinschert
  • M. Zenker
  • G. Rosenberger
  • K. Kutsche



Die Exomanalyse ist als Methode zur Identifizierung von pathogenen Sequenzvarianten bei Patienten mit einem nach den mendelschen Regeln vererbten Krankheitsbild nicht mehr wegzudenken. Sie bildet umfassend die codierenden Sequenzen eines Genoms ab und ist schnell und kostengünstig.


Da die technischen Schwierigkeiten bei der Durchführung der Exomsequenzierung inzwischen weitgehend gelöst sind, stellt die Auswertung der großen Datenmenge und somit das Finden der pathogenen Sequenzvariante inmitten 10.000er Sequenzabweichungen die eigentliche Herausforderung dar. Dies kann nur mithilfe einer bioinformatischen Filterung der Daten erfolgen, die jeweils unter Berücksichtigung der in die Analyse einbezogenen Patienten und Familienmitglieder sowie des wahrscheinlichsten Erbganges angepasst werden muss.


Anhand von 4 Fallbeispielen werden verschiedene Priorisierungsstrategien für die Filterung der Sequenzvarianten vorgestellt, die jeweils zur Identifikation der wahrscheinlich pathogenen Veränderung bei dem jeweiligen Indexpatienten geführt haben.


Hochdurchsatznukleotidsequenzierung Exom Variantenpriorisierung Mendelsche Krankheit Molekulare Diagnostik 

Exome sequencing for identification of disease genes for rare syndromes

Experience from Hamburg, Germany



Whole exome sequencing (WES) is the state-of-the-art method for identification of pathogenic mutations in patients with a Mendelian disorder. WES comprehensively covers the coding sequence of the genome and is a fast and cost-effective technique.


As most of the technical difficulties have been overcome for WES, the major issue is data processing and analysis to find the pathogenic sequence variation among tens of thousands of sequence changes. Bioinformatic analysis pipelines for filtering sequence variants have to be adapted according to the patients and family members examined by WES and the most likely inheritance pattern underlying the disease.

Possible approaches

Based on 4 cases, different variant prioritization strategies which led to identification of the most likely causative changes in the index patients are described.


High-throughput nucleotide sequencing Exome Variant prioritization Mendelian disorder Molecular diagnostics 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • F. Kortüm
    • 1
  • H. Abdollahpour
    • 1
    • 2
  • M. Alawi
    • 3
    • 4
  • G.C. Korenke
    • 5
  • E. Seemanova
    • 6
  • S. Tinschert
    • 7
    • 8
  • M. Zenker
    • 9
  • G. Rosenberger
    • 1
  • K. Kutsche
    • 1
  1. 1.Institut für HumangenetikUniversitätsklinikum Hamburg-EppendorfHamburgDeutschland
  2. 2.Aktuelle Adresse: MVZ genteQ GmbHHamburgDeutschland
  3. 3.Bioinformatics Service FacilityUniversitätsklinikum Hamburg-EppendorfHamburgDeutschland
  4. 4.Leibniz-Institut für Experimentelle Virologie, Virus GenomikHeinrich-Pette-InstitutHamburgDeutschland
  5. 5.Zentrum für Kinder- und Jugendmedizin, NeuropädiatrieKlinikum OldenburgOldenburgDeutschland
  6. 6.Department of Clinical Genetics, Institute of Biology and Medical GeneticsUniversity Hospital Motol, Second Medical School, Charles University PraguePragueTschechische Republik
  7. 7.Sektion für Humangenetik, Department für Medizinische Genetik, Molekulare und Klinische PharmakologieMedizinische Universität InnsbruckInnsbruckÖsterreich
  8. 8.Institut für Klinische GenetikMedizinische Fakultät Carl Gustav Carus, TU DresdenDresdenDeutschland
  9. 9.Institut für HumangenetikOtto-von-Guericke-Universität MagdeburgMagdeburgDeutschland

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