Mutiple DICER1-related lesions associated with a germline deep intronic mutation

Pediatr Blood Cancer. 2018 Jun;65(6):e27005. doi: 10.1002/pbc.27005. Epub 2018 Feb 22.

Abstract

Germline DICER1 pathogenic variants predispose to numerous benign and malignant tumors. In this report, we describe DICER1 gene analysis in an adolescent diagnosed with multinodular goiter, ovarian Sertoli-Leydig cell tumor, and lung cyst. DICER1 mutational screening at the DNA level failed to detect any pathogenic variant. Subsequent messenger RNA (mRNA) analysis revealed a 132 nucleotide intronic sequence exonization. This truncating event was caused by a deep intronic mutation generating a de novo acceptor splice site. This study demonstrates that some undetected DICER1 mutations should be investigated at the mRNA level.

Keywords: DICER1; cryptic exon; deep intronic mutation; lung cyst; multinodular goiter; ovarian Sertoli-Leydig cell tumor.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Aged
  • Child
  • DEAD-box RNA Helicases / genetics*
  • Female
  • Germ-Line Mutation*
  • Goiter, Nodular / genetics*
  • Goiter, Nodular / pathology
  • Humans
  • Introns / genetics*
  • Lung Diseases / genetics*
  • Lung Diseases / pathology
  • Male
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Pedigree
  • Prognosis
  • Ribonuclease III / genetics*
  • Sertoli-Leydig Cell Tumor / genetics*
  • Sertoli-Leydig Cell Tumor / pathology

Substances

  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases

Supplementary concepts

  • Euthyroid Goiter