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A novel MSH2 germline mutation in a Druze HNPCC family

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Abstract

Germline mutations in DNA mismatch repair (DNA-MMR) genes, mainly MLH1, MSH2, and MSH6, underlie Hereditary non-polyposis colorectal cancer (HNPCC) and are mostly family-specific, with few reported founder mutations in MSH2 (Ashkenazim) MLH1 (Finnish). No mutations in colon cancer susceptibility genes have ever been reported in Druze individuals, a Moslem related faith encompassing ∼1,000,000 individuals worldwide. A novel MSH2 mutation is described in a Druze HNPCC family: a multigenerational family with 10 members in 4 generations affected with colorectal cancer (mean age of diagnosis 46.5 years), two with gastric cancer and one—endometrial cancer. Mutational analysis of the MSH2 gene using denaturing gradient gel electrophoresis (DGGE) and direct sequencing revealed the c.702delA mutation in codon 234 of exon 4 of the MSH2 gene leading to a premature early stop in codon 245, p.Thr234fsX245. Analysis of mutation-carrying or presumed carriers individuals’ offspring, revealed 11/42 asymptomatic mutation carriers, age range 17–50 years. The mutation was not present in two additional Druze HNPCC families and 20 Druze sporadic colon cancer patients. This is the first mutation ever reported in a colon cancer susceptibility gene in a Druze family and it appears not to be a founder mutation in Druze individuals with HNPCC.

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Acknowledgements

This work was in part sponsored by a grant from the Israel cancer association (ICA) to E.F.; This work was done in part as fulfillment for the studies for a graduate degree from the University of Groningen, The Netherlands by Renée C. Niessen.

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Authors and Affiliations

  1. Oncology Unit, Rivkah Ziv Medical Center, Zefat, Israel

    Jamal Zidan

  2. The Bruce Rappaport School of Medicine, The Technion, Haifa, Israel

    Jamal Zidan

  3. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Renée C. Niessen, Dennie Rozeveld & Robert M. W. Hofstra

  4. Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel

    Yael Laitman & Eitan Friedman

  5. The Sackler School of Medicine, Tel-Aviv University, Ramat Aviv, Israel

    Eitan Friedman

Authors
  1. Jamal Zidan
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  2. Renée C. Niessen
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  3. Yael Laitman
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  4. Dennie Rozeveld
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  5. Robert M. W. Hofstra
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  6. Eitan Friedman
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Correspondence to Eitan Friedman.

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Zidan, J., Niessen, R.C., Laitman, Y. et al. A novel MSH2 germline mutation in a Druze HNPCC family. Familial Cancer 7, 135–139 (2008). https://doi.org/10.1007/s10689-007-9157-5

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  • DOI: https://doi.org/10.1007/s10689-007-9157-5

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