Germline MSH2 and MLH1 mutational spectrum including large rearrangements inHNPCC families from Poland (update study).
Journal Title: Clinical Genetics - Year 2006, Vol 69, Issue 1
Abstract
Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 accountfor a significant proportion of hereditary non-polyposis colorectal cancer (HNPCC) families. One approachby which development of an efficient DNA-testing procedure can be implemented is to describe the natureand frequency of common mutations in particular ethnic groups. Two hundred and twenty-six patients fromfamilies matching the Amsterdam II diagnostic criteria or suspected HNPCC criteria were screened forMSH2 and MLH1 germline mutations. Fifty different pathogenic mutations were found, 25 in MSH2 and 25in MLH1. Twenty-four of these had not previously been described in other populations. Among our 78 familieswith MSH2 or MLH1 mutations, 54 (69.2%) were affected by recurrent mutations including 38 found at leasttwice in our own series. Two of the most frequent alterations were a substitution of A to T at the splicedonor 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 amplificationassay, exon 9 deletions in the MSH2 gene were found in two families. Our results indicate that a screeningprotocol specific for the Polish population that is limited to the detection of all reported mutationswill result in the identification of the majority of changes present in MLH1 and MSH2 genes in PolishHNPCC kindreds.
Authors and Affiliations
G Kurzawski, J Suchy, M Lener, E Kłujszo-Grabowska, K Safranow, A Jakubowska, T Huzarski, C Cybulski, O Oszurek, D Oszutowska, S Góźdź, R Słomski, Ł Fiszer-Maliszewska, M M Sasiadek, Z Grzebieniak, P Richter, I Brozek, B Wysocka, H Janiszewska, R J Scott
Keywords
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Germline MSH2 and MLH1 mutational spectrum including large rearrangements inHNPCC families from Poland (update study).
Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 accountfor a significant proportion of hereditary non-polyposis colorectal cancer (HNPCC) families. One approachby which development of an efficient DNA-t...