Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study)
| Autor: | Katarzyna Jakubowska, Józef Kładny, Barbara Wysocka, Janina Suchy, D. Sorokin, S Niepsuj, Zbigniew Banaszkiewicz, Cezary Cybulski, Marek Bębenek, MM Sąsiadek, E Kowalska, Andrzej Pławski, P Richter, Małgorzata Stawicka, A Łącka-Wojciechowska, Dariusz Godlewski, Jerzy Kowalczyk, Hanna Janiszewska, Tadeusz Dębniak, Grzegorz Kurzawski, Oleg Oszurek, Izabela Brozek, Marcin Lener, Jacek Gronwald, Ewa Klujszo-Grabowska, Rodney J. Scott, Jakub Lubiński, Krzysztof Safranow, Andrzej Rozmiarek, Z Grzebieniak, Tomasz Byrski, Anna Jakubowska, Ryszard Słomski, D Czudowska, Agnieszka Stembalska, Dorota Oszutowska, Tomasz Huzarski, E. Kilar, Arkadiusz Jawień, Stanisław Góźdź, Ł Fiszer-Maliszewska, Janusz Limon |
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| Rok vydání: | 2005 |
| Předmět: |
Genetics
congenital hereditary and neonatal diseases and abnormalities Mutation nutritional and metabolic diseases Biology medicine.disease_cause MLH1 digestive system diseases Germline Germline mutation MSH2 medicine Missense mutation DNA mismatch repair Multiplex ligation-dependent probe amplification neoplasms Genetics (clinical) |
| Zdroj: | Clinical Genetics. 69:40-47 |
| ISSN: | 0009-9163 |
| DOI: | 10.1111/j.1399-0004.2006.00550.x |
| Popis: | Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 account for a significant proportion of hereditary non-polyposis colorectal cancer (HNPCC) families. One approach by which development of an efficient DNA-testing procedure can be implemented is to describe the nature and frequency of common mutations in particular ethnic groups. Two hundred and twenty-six patients from families matching the Amsterdam II diagnostic criteria or suspected HNPCC criteria were screened for MSH2 and MLH1 germline mutations. Fifty different pathogenic mutations were found, 25 in MSH2 and 25 in MLH1. Twenty-four of these had not previously been described in other populations. Among our 78 families with MSH2 or MLH1 mutations, 54 (69.2%) were affected by recurrent mutations including 38 found at least twice in our own series. Two of the most frequent alterations were a substitution of A to T at the splice donor site of intron 5 of MSH2 and a missense change (A681T) of MLH1 found in 10 and eight families, respectively. Among large deletions detected by the multiplex ligation-dependent probe amplification assay, exon 9 deletions in the MSH2 gene were found in two families. Our results indicate that a screening protocol specific for the Polish population that is limited to the detection of all reported mutations will result in the identification of the majority of changes present in MLH1 and MSH2 genes in Polish HNPCC kindreds. |
| Databáze: | OpenAIRE |
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