TY - JOUR
T1 - A novel MSH2 germline mutation in a Druze HNPCC family
AU - Zidan, Jamal
AU - Niessen, Renée C.
AU - Laitman, Yael
AU - Rozeveld, Dennie
AU - Hofstra, Robert M.W.
AU - Friedman, Eitan
N1 - Funding Information:
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.
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
KW - DGGE
KW - Druze faith
KW - Germline mutations
KW - HNPCC
KW - Inherited predisposition to colon cancer
KW - MSH2 gene
UR - http://www.scopus.com/inward/record.url?scp=45749142471&partnerID=8YFLogxK
U2 - 10.1007/s10689-007-9157-5
DO - 10.1007/s10689-007-9157-5
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C2 - 17661183
AN - SCOPUS:45749142471
SN - 1389-9600
VL - 7
SP - 135
EP - 139
JO - Familial Cancer
JF - Familial Cancer
IS - 2
ER -
