Abstract
Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by a deficiency in DNA mismatch repair in consequence of germline mutations mainly in the genes MSH2 and MLH1. Around 10% of patients suspected of HNPCC are identified with large genomic deletions that cannot be detected by conventional methods of mutation screening. The recently developed multiplex ligation-dependent probe amplification (MLPA) proved to be an easy to perform method for deletion detection and is reliable when more than one exon is deleted. We show that, in some cases, apparent deletions of single exons may actually result from single base substitutions or small insertions/deletions in the hybridisation sequence of MLPA probes. We conclude that single exon deletions, detected by MLPA or multiplex PCR, should be validated with additional methods.
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Acknowledgements
We thank the patients who have participated in this study. The work of the German HNPCC Consortium is supported by a multicentre grant from the Deutsche Krebshilfe, Bonn, Germany, Project No.: 70-3027-Ma1.
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Wehner, M., Mangold, E., Sengteller, M. et al. Hereditary nonpolyposis colorectal cancer: pitfalls in deletion screening in MSH2 and MLH1 genes. Eur J Hum Genet 13, 983–986 (2005). https://doi.org/10.1038/sj.ejhg.5201421
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DOI: https://doi.org/10.1038/sj.ejhg.5201421
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