Communicated by Haig H. Kazazian, Jr.
Insertion of an SVA element, a nonautonomous retrotransposon, in PMS2 intron 7 as a novel cause of lynch syndrome†
Article first published online: 30 APR 2012
© 2012 Wiley Periodicals, Inc.
Volume 33, Issue 7, pages 1051–1055, July 2012
How to Cite
van der Klift, H. M., Tops, C. M., Hes, F. J., Devilee, P. and Wijnen, J. T. (2012), Insertion of an SVA element, a nonautonomous retrotransposon, in PMS2 intron 7 as a novel cause of lynch syndrome. Hum. Mutat., 33: 1051–1055. doi: 10.1002/humu.22092
- Issue published online: 5 JUN 2012
- Article first published online: 30 APR 2012
- Accepted manuscript online: 27 MAR 2012 09:42AM EST
- Manuscript Accepted: 8 MAR 2012
- Manuscript Received: 30 OCT 2011
- Lynch syndrome;
- LINE-1-mediated retrotransposition;
Heterozygous germline mutations in the mismatch repair gene PMS2 predispose carriers for Lynch syndrome, an autosomal dominant predisposition to cancer. Here, we present a LINE-1-mediated retrotranspositional insertion in PMS2 as a novel mutation type for Lynch syndrome. This insertion, detected with Southern blot analysis in the genomic DNA of the patient, is characterized as a 2.2 kb long 5′ truncated SVA_F element. The insertion is not detectable by current diagnostic testing limited to MLPA and direct Sanger sequencing on genomic DNA. The molecular nature of this insertion could only be resolved in RNA from cultured lymphocytes in which nonsense-mediated RNA decay was inhibited. Our report illustrates the technical problems encountered in the detection of this mutation type. Especially large heterozygous insertions will remain unnoticed because of preferential amplification of the smaller wild-type allele in genomic DNA, and are probably underreported in the mutation spectra of autosomal dominant disorders. Hum Mutat 33:1051–1055, 2012. © 2012 Wiley Periodicals, Inc.