A novel MSH2 germline mutation in a Druze HNPCC family

Jamal Zidan, Renée C. Niessen, Yael Laitman, Dennie Rozeveld, Robert M.W. Hofstra, Eitan Friedman

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)135-139
Number of pages5
JournalFamilial Cancer
Volume7
Issue number2
DOIs
StatePublished - Jun 2008

Keywords

  • DGGE
  • Druze faith
  • Germline mutations
  • HNPCC
  • Inherited predisposition to colon cancer
  • MSH2 gene

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