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BioMed Research International
Volume 2013 (2013), Article ID 219897, 7 pages
Research Article

Contribution of Large Genomic Rearrangements in Italian Lynch Syndrome Patients: Characterization of a Novel Alu-Mediated Deletion

1Dipartmento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini, 5 80131 Napoli, Italy
2Dipartimento di Discipline Chirurgiche ed Oncologiche, Università degli Studi di Palermo, Via Liborio Giuffrè, 90127 Palermo, Italy
3Department of Biochemistry and Medical Biotechnology and CEINGE-Biotecnologie Avanzate, Università degli Studi di Napoli Federico II, Via Pansini, 5 80131 Napoli, Italy

Received 10 October 2012; Accepted 20 November 2012

Academic Editor: Francesco Baudi

Copyright © 2013 Francesca Duraturo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR) genes, mainly MLH1 and MSH2. Most of the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangements in the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied on average from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2 genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenic point mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6 in one of the patients analysed (1.6% frequency). This deletion was confirmed and localised by long-range PCR. The breakpoints of this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement was a product of Alu-mediated recombination. Our findings identified a novel Alu-mediated rearrangement within MSH2 gene and showed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italian patients with an inherited predisposition to colon cancer.