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Familial Cancer

, Volume 5, Issue 2, pp 195–199 | Cite as

A ‘Nonsense’ Mutation Leads to Aberrant Splicing of hMLH1 in a German Hereditary Non-polyposis Colorectal Cancer Family

  • J. Baehring
  • C. Sutter
  • M. Kadmon
  • M. V. Knebel Doeberitz
  • J. GebertEmail author
Article

Abstract

Hereditary Non-polyposis Colorectal Cancer (HNPCC) is an autosomal dominant cancer predisposition syndrome caused by germline mutations in at least four genes encoding integral components of the cellular DNA mismatch repair (MMR) system. The spectrum of genetic alterations encompasses missense- and nonsense mutations, intronic mutations affecting splice donor or acceptor sites as well as small-scale deletions and insertions. We have identified a ‘nonsense’ mutation that activates a cryptic splice site generating an in frame deletion of the last 17 codons of exon1 of the hMLH1 gene causing HNPCC in a German family. We present a comprehensive genetic analysis of this family that demonstrates important aspects of HNPCC pathogenesis.

Key words

aberrant splicing hMLH1 hMSH2 HNPCC nonsense mutation splice donor site 

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Copyright information

© Springer 2006

Authors and Affiliations

  • J. Baehring
    • 1
    • 3
  • C. Sutter
    • 2
    • 4
  • M. Kadmon
    • 1
  • M. V. Knebel Doeberitz
    • 2
  • J. Gebert
    • 2
    Email author
  1. 1.Department of General SurgeryUniversity of HeidelbergHeidelbergGermany
  2. 2.Division of Molecular PathologyInstitute of Pathology, University of HeidelbergHeidelbergGermany
  3. 3.Departments of Neurology and NeurosurgeryYale University School of MedicineNew HavenUSA
  4. 4.Department of Human GeneticsInstitute of Human Genetics, University of HeidelbergHeidelbergGermany

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