First report of a de novo germline mutation in the MLH1 gene
| Autor: | Huub J C van der Mijle, Bart Mol, Monique de Raad, Arend Karrenbeld, Yvonne J. Vos, Rolf H. Sijmons, Rein P. Stulp |
|---|---|
| Přispěvatelé: | Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male de novo congenital hereditary and neonatal diseases and abnormalities MICROSATELLITE INSTABILITY DATABASE DNA Mutational Analysis HNPCC INTERNATIONAL-COLLABORATIVE-GROUP Case Report Biology Gene mutation MLH1 LYNCH-SYNDROME Germline Germline mutation medicine Humans Germ-Line Mutation Adaptor Proteins Signal Transducing Genetics Base Sequence Gastroenterology Nuclear Proteins General Medicine DNA DNA Neoplasm medicine.disease Colorectal Neoplasms Hereditary Nonpolyposis Lynch syndrome digestive system diseases MSH6 germline mutation MSH2 Mutation (genetic algorithm) UPDATE Carrier Proteins MutL Protein Homolog 1 |
| Zdroj: | World Journal of Gastroenterology, 12(5), 809-811. Baishideng Publishing Group Inc. |
| ISSN: | 1007-9327 |
| Popis: | Hereditary non-polyposis colorectal carcinoma (HNPCC) is an autosomal dominant disorder associated with colorectal and endometrial cancer and a range of other tumor types. Germline mutations in the DNA mismatch repair (MMR) genes, particularly MLH1, MSH2, and MSH6, underlie this disorder. The vast majority of these HNPCC-associated mutations have been proven, or assumed, given the family history of cancer, to be transmitted through several generations. To the best of our knowledge, only a single case of a de novo germline MMR gene mutation (in MSH2) has been reported till now. Here, we report a patient with a de novo mutation in MLH1. We identified a MLH1 Q701X truncating mutation in the blood lymphocytes of a male who had been diagnosed with rectal cancer at the age of 35. His family history of cancer was negative for the first- and second-degree relatives. The mutation could not be detected in the patient' parents and sibling and paternity was confirmed with a set of highly polymorphic markers. Non-penetrance and small family size is the common explanation of verified negative family histories of cancer in patients with a germline MMR gene mutation. However, in addition to some cases explained by non-paternity, de novo germline mutations should be considered as a possible explanation as well. As guidelines that stress not to restrict MMR gene mutation testing to patients with a positive family history are more widely introduced, more cases of de novo MMR gene germline mutations may be revealed. |
| Databáze: | OpenAIRE |
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