NovelMLH1andMSH2germline mutations in the first HNPCC families identified in Slovakia
| Autor: | Palaj J, Margita Lukacova, Peter Hlavcak, Bujalkova M, Andrej Böör, Denisa Ilencikova, Zdena Bartosova, Ritva Haider, Brigitte Wolf, Josef Jiricny, Ivana Fridrichova, Ludovit Lukac, Giancarlo Marra, Minna Nyström-Lahti, Peter Krizan |
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| Rok vydání: | 2003 |
| Předmět: |
Genetics
congenital hereditary and neonatal diseases and abnormalities 0303 health sciences Amsterdam criteria Mutation nutritional and metabolic diseases Cancer Biology medicine.disease medicine.disease_cause MLH1 digestive system diseases 3. Good health 03 medical and health sciences 0302 clinical medicine Germline mutation MSH2 030220 oncology & carcinogenesis Genotype medicine Missense mutation Genetics (clinical) 030304 developmental biology |
| Zdroj: | Human Mutation. 21:449-449 |
| ISSN: | 1059-7794 |
| DOI: | 10.1002/humu.9127 |
| Popis: | Hereditary nonpolyposis colorectal cancer (HNPCC) is a dominantly-inherited cancer predisposition syndrome, in which the susceptibility to cancer of the colon, endometrium and ovary is linked to germline mutations in DNA mismatch repair (MMR) genes. We have recently initiated a cancer prevention program in suspected HNPCC families in the Slovak Republic. The first ten families fulfilling Amsterdam criteria or Bethesda guidelines were screened for germline mutations in MLH1 and MSH2, two MMR genes most frequently mutated in HNPCC families. Six mutations were identified, five of which have not been reported previously. Two of the three new mutations in MLH1 (c.380+2T>A; c.307-2A>C) were absent from 100 chromosomes of healthy controls and probably cause a splicing defect, while the third was a 1 bp deletion (c.1261delA). In the MSH2 gene, one new nonsense (c.1030C>T [p.Q344X]) and one missense (c.524T>C [p.L175P]) mutation were identified. This latter variant was not found in 104 alleles of healthy control individuals. Moreover, a previously-reported pathogenic mutation (c.677G>T [p.R226L]) was found in one kindred. The clinical data and the genotypic and phenotypic evaluation of the tumors indicate that all the new alterations are pathogenic HNPCC mutations. |
| Databáze: | OpenAIRE |
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