Putative common origin of two MLH1 mutations in Italian-Quebec hereditary non-polyposis colorectal cancer families

I. Thiffault, William D. Foulkes, V. A. Marcus, D. Farber, L. Kasprzak, E. MacNamara, N. Wong, P. Hutter, P. Radice, L. Bertario, G. Chong

Research output: Contribution to journalArticle

Abstract

Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common inherited cancer syndromes, accounting for 3-5% of all cases of colorectal cancer. In most HNPCC families, the disease is caused by a germline mutation in MLH1 or MSH2. In some populations, founder mutations appear to explain a substantial fraction of HNPCC. We report here the identification and preliminary characterization of two putative MLH1 founder mutations. The mutation MLH1c.1831delAT was shown to segregate in two Quebec families of Italian origin who fulfilled the Amsterdam criteria for HNPCC. Haplotype analysis using five intragenic microsatellite/single nucleotide polymorphism markers spanning MLH1 on chromosome 3 showed that these two unrelated families share an identical haplotype. In addition, two other Italian kindred whose affected members carry MLH1g.IVS6+3A>G also share a common haplotype, suggesting that, similarly, the latter mutation has a common origin. These mutations are the first putative founder MLH1 mutations to be identified in HNPCC kindred of Italian origin.

Original languageEnglish
Pages (from-to)137-143
Number of pages7
JournalClinical Genetics
Volume66
Issue number2
DOIs
Publication statusPublished - Aug 2004

Keywords

  • Colorectal cancer
  • Founder mutation
  • HNPCC
  • Italian
  • MLH1
  • Quebec

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Thiffault, I., Foulkes, W. D., Marcus, V. A., Farber, D., Kasprzak, L., MacNamara, E., Wong, N., Hutter, P., Radice, P., Bertario, L., & Chong, G. (2004). Putative common origin of two MLH1 mutations in Italian-Quebec hereditary non-polyposis colorectal cancer families. Clinical Genetics, 66(2), 137-143. https://doi.org/10.1111/j.1399-0004.2004.00274.x