Liccardo Raffaella, De Rosa Marina, Rossi Giovanni Battista, Rigler Gabriele, Izzo Paola, Duraturo Francesca
Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", 80131 Naples, Italy.
Endoscopy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione Giovanni Pascale" IRCCS, 80131 Naples, Italy.
Cancer Genet. 2018 Feb;221:19-24. doi: 10.1016/j.cancergen.2017.11.008. Epub 2017 Dec 27.
Lynch syndrome (LS) is associated with germ-line mutations in the DNA mismatch repair (MMR) genes, mainly MLH1, MSH2, MSH6, and PMS2. Most of genetic variants in the MMR genes predisposing to LS are point mutations, small deletions and insertions but large genomic rearrangements in the MMR genes also predisposing to Lynch syndrome. In this study, we report a novel, large rearrangement of the MSH2 gene, manifested by a duplication spanning a 14,846-bps region from intron 7 through intron 9. The breakpoints of this rearrangement were characterized by sequencing. Further analysis of the breakpoints revealed that this rearrangement was a product of Alu-mediated recombination. Finally, this large duplication was identified in three unrelated patients. Breakpoint analysis revealed the same junction fragments of introns 7 and 8 in the three index cases, suggesting a recurrent duplication or, alternatively, identity of the respective alleles by descent.
林奇综合征（LS）与DNA错配修复（MMR）基因的种系突变有关，主要是MLH1、MSH2、MSH6和PMS2。MMR基因中大多数易患LS的遗传变异是点突变、小缺失和插入，但MMR基因中的大基因组重排也易患林奇综合征。在本研究中，我们报告了一种新的、MSH2基因的大重排，表现为从第7内含子到第9内含子跨越14846个碱基对区域的重复。通过测序对这种重排的断点进行了表征。对断点的进一步分析表明，这种重排是Alu介导的重组产物。最后，在三名无关患者中发现了这种大重复。断点分析显示，三名索引病例中第7和第8内含子的连接片段相同，提示存在反复重复，或者通过遗传各自等位基因相同。
