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

Genes Chromosomes Cancer. 2021 Aug;60(8):571-576. doi: 10.1002/gcc.22950. Epub 2021 Apr 21.

Abstract

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 in exon 12 of MSH2 in an individual with early-onset colorectal cancer and a very strong LS family history. RT-PCR analysis indicated a larger aberrant MSH2 transcript in one of the family members. MSK-IMPACT next-generation sequencing and long-range PCR analyses 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. This variant also segregated with LS related cancers in four affected family members in this family. Based on this evidence, this MSH2 SVA insertion is considered pathogenic.

Keywords: Lynch syndrome; MSH2; SVA; germline.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alu Elements*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • Humans
  • Male
  • Middle Aged
  • Minisatellite Repeats*
  • MutS Homolog 2 Protein / genetics*

Substances

  • MSH2 protein, human
  • MutS Homolog 2 Protein