Putative common origin of two MLH1 mutations in Italian-Quebec hereditary non-polyposis colorectal cancer families
| Autor: | I, Thiffault, W D, Foulkes, V A, Marcus, D, Farber, L, Kasprzak, E, MacNamara, N, Wong, P, Hutter, P, Radice, L, Bertario, G, Chong |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Quebec Nuclear Proteins Sequence Analysis DNA Middle Aged Colorectal Neoplasms Hereditary Nonpolyposis Immunohistochemistry Founder Effect Neoplasm Proteins Pedigree Evolution Molecular Haplotypes Italy Mutation Humans Carrier Proteins MutL Protein Homolog 1 Adaptor Proteins Signal Transducing Microsatellite Repeats |
| Zdroj: | Clinical genetics. 66(2) |
| ISSN: | 0009-9163 |
| Popis: | 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 + 3AG 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. |
| Databáze: | OpenAIRE |
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