Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR) genes, mainly MLH1 and MSH2. Mostof the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangementsin the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied onaverage from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenicpoint mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6in one of the patients analysed (1.6% frequency). This deletion was confirmed and localised by long-range PCR. The breakpointsof this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement wasa product of Alu-mediated recombination. Our fndings identified a novel Alu-mediated rearrangement within MSH2 gene andshowed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italianpatients with an inherited predisposition to colon cancer.
|Numero di pagine||0|
|Rivista||BioMed Research International|
|Stato di pubblicazione||Published - 2013|
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