RNA sequencing uncovers clinically actionable germline intronic MSH2 variants in previously unresolved Lynch syndrome families

BMJ Case Rep. 2022 Apr 29;15(4):e249580. doi: 10.1136/bcr-2022-249580.

Abstract

Despite advances in genetic testing for Lynch syndrome, nearly one quarter of mismatch repair-deficient (MMRd) colorectal and endometrial cancers remain unexplained. When added to germline DNA testing, RNA sequencing can increase diagnostic yield, improve variant classification and reduce variants of uncertain significance. Here, we describe two cases where RNA sequencing uncovered likely pathogenic MSH2 variants in families with MMRd tumours that were initially unexplained following comprehensive genetic testing for Lynch syndrome.

Keywords: Genetic screening / counselling; Oncology.

Publication types

  • Case Reports

MeSH terms

  • Colorectal Neoplasms, Hereditary Nonpolyposis* / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
  • Female
  • Germ Cells
  • Humans
  • MutS Homolog 2 Protein / genetics
  • RNA
  • Sequence Analysis, RNA

Substances

  • RNA
  • MSH2 protein, human
  • MutS Homolog 2 Protein