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Putative common origin of two MLH1 mutations in Italian‐Quebec hereditary non‐polyposis colorectal cancer families
Author(s) -
Thiffault I,
Foulkes WD,
Marcus VA,
Farber D,
Kasprzak L,
MacNamara E,
Wong N,
Hutter P,
Radice P,
Bertario L,
Chong G
Publication year - 2004
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2004.00274.x
Subject(s) - mlh1 , genetics , haplotype , msh2 , biology , germline mutation , founder effect , mutation , lynch syndrome , dna mismatch repair , cancer , colorectal cancer , gene , allele
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 MLH1 c.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 MLH1 g.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.