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.