Insertion of an SVA element in MSH2 as a novel cause of Lynch syndrome

• DOI: 10.1002/gcc.22950
• Publication Date: 2021-04-06T11:54:53Z
• Authors: Ciyu Yang; Yirong Li; Magan Trottier; Michael P. Farrell; Vikas K. Rai; Erin E. Salo‐Mullen; David J. Gallagher; Zsofia K. Stadler; Heleen M. van der...; Liying Zhang
• Keywords: MSH2; Lynch Syndrome; Retrotransposon; Alu element; PALB2

Germline mutations in the DNA mismatch repair (MMR) genes cause Lynch syndrome (LS). In this study, we identified and characterized a novel SINE-VNTR-Alu (SVA) insertion exon 12 of MSH2 an individual with early-onset colorectal cancer very strong LS family history. RT-PCR analysis indicated larger aberrant transcript one members. MSK-IMPACT next-generation sequencing long-range PCR analyses revealed at c.1972 position antisense orientation. The was further as SVA element approximately 3 kb length, belonging to SVA_F1 retrotransposons. This variant also segregated related cancers four affected members family. Based on evidence, is considered pathogenic.