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Genomic Deletions in MSH2 or MLH1 Are a Frequent Cause of Hereditary Non-Polyposis Colorectal Cancer: Identification of Novel and Recurrent Deletions by MLPA

Lookup NU author(s): Professor Sir John BurnORCiD


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Gene dosage abnormalities account for a significant proportion of the mutations in genes tested in DNA diagnostic laboratories. Detection of these changes has proved a challenge as the methods available to date are time consuming or unreliable. The multiplex ligation-dependant probe assay (MLPA) is a new technique allowing relative quantification of up to 40 different nucleic acid sequences in a single reaction tube. We have evaluated MLPA for potential use in the diagnostic setting against the following criteria: accuracy, reagent cost, hands-on time, reliability, and retests required. A total of 215 UK patients referred for genetic testing on the basis of a family history consistent with autosomal dominant hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) were tested by MLPA. Of these, 12 cases with deletions of one or more exons were identified, six with MLH1 deletions and six with MSH2 deletions. Test failure rates were less than 5% and overall mutation detection sensitivity in this series was increased by approximately 50% by the inclusion of MLPA for an additional testing cost of about 10%. Two novel mutations in MSH2 and 10 novel point mutations in MLH1 were also identified during the course of this study. We conclude that MLPA is a cost effective and robust gene dosage method that can be readily adopted by diagnostic services. Comprehensive mutation scanning for MSH2 and MLH1 is incomplete without gene dosage analysis. © 2003 Wiley-Liss, Inc.

Publication metadata

Author(s): Taylor CF, Charlton RS, Burn J, Sheridan E, Taylor GR

Publication type: Article

Publication status: Published

Journal: Human Mutation

Year: 2003

Volume: 22

Issue: 6

Pages: 428-433

ISSN (print): 1059-7794

ISSN (electronic): 1098-1004

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/humu.10291

PubMed id: 14635101


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