Pedigree and genetic analysis of a novel mutation carrier patient suffering from hereditary nonpolyposis colorectal cancer

World J Gastroenterol. 2006 Feb 28;12(8):1192-7. doi: 10.3748/wjg.v12.i8.1192.


Aim: To screen a suspected Hungarian HNPCC family to find specific mutations and to evaluate their effect on the presentation of the disease.

Methods: The family was identified by applying the Amsterdam and Bethesda Criteria. Immunohistochemistry was performed, and DNA samples isolated from tumor tissue were evaluated for microsatellite instability. The identification of possible mutations was carried out by sequencing the hMLH1 and hMSH2 genes.

Results: Two different mutations were observed in the index patient and in his family members. The first mutation was located in exon 7, codon 422 of hMSH2, and caused a change from Glu to STOP codon. No other report of such a mutation has been published, as far as we could find in the international databases. The second mutation was found in exon 3 codon 127 of the hMSH2 gene, resulting in Asp-->Ser substitution. The second mutation was already published, as a non-pathogenic allelic variation.

Conclusion: The pedigree analysis suggested that the newly detected nonsense mutation in exon 7 of the hMSH2 gene might be responsible for the development of colon cancers. In family members where the exon 7 mutation is not coupled with this missense mutation, colon cancer appears after the age of 40. The association of these two mutations seems to decrease the age of manifestation of the disease into the early thirties.

Publication types

  • Case Reports

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Carrier Proteins / analysis
  • Carrier Proteins / genetics
  • Child, Preschool
  • Colorectal Neoplasms, Hereditary Nonpolyposis / chemistry
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / genetics
  • Exons / genetics
  • Female
  • Genetic Testing
  • Heterozygote*
  • Humans
  • Immunohistochemistry
  • Infant
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / analysis
  • MutS Homolog 2 Protein / genetics
  • Mutation*
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics
  • Pedigree*
  • Polymorphism, Single-Stranded Conformational


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA, Neoplasm
  • MLH1 protein, human
  • Nuclear Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein