Abstract
Germline mutations in the DNA mismatch repair (MMR) genes cause Lynch
syndrome (LS). Insertions of retrotransposons in MMR genes have been
reported as a rare cause of LS. Here, we present a novel SINE-VNTR-Alu
(SVA) insertion in exon 12 of MSH2 in an individual with early-onset
colorectal cancer and strong LS family history. RT-PCR analysis
indicated a larger aberrant MSH2 transcript in one of the family
members. MSK-IMPACT next-generation sequencing testing and long-range
PCR revealed an insertion in MSH2 exon 12 at the c.1972 position in an
antisense orientation. The insertion was further characterized as an SVA
element approximately 3 kb in length, belonging to the SVA_F1 family of
retrotransposons.