The Pathogenic RET Val804Met Variant in Acromegaly: A New Clinical Phenotype?

Int J Mol Sci. 2024 Feb 5;25(3):1895. doi: 10.3390/ijms25031895.

Abstract

Several genetic investigations were conducted to identify germline and somatic mutations in somatotropinomas, a subtype of pituitary tumors. To our knowledge, we report the first acromegaly patient carrying a RET pathogenic variant: c.2410G>A (rs79658334), p.Val804Met. Alongside the fact that the patient's father and daughter carried the same variant, we investigated the clinical significance of this variant in the context of somatotropinomas and other endocrine tumors, reviewing the RET mutations' oncogenic mechanisms. The aim was to search for new targets to precisely manage and treat acromegaly. Our case describes a new phenotype associated with the RET pathogenic variant, represented by aggressive acromegaly, and suggests consideration for RET mutation screening if NGS for well-established PitNET-associated gene mutations renders negative.

Keywords: RET mutation; acromegaly; genetics; hereditary cancer-predisposing syndrome; precision medicine.

Publication types

  • Case Reports

MeSH terms

  • Acromegaly* / genetics
  • Germ-Line Mutation
  • Humans
  • Multiple Endocrine Neoplasia Type 2a / genetics
  • Mutation
  • Phenotype
  • Proto-Oncogene Proteins c-ret* / genetics
  • Thyroid Neoplasms / genetics

Substances

  • Proto-Oncogene Proteins c-ret
  • RET protein, human

Grants and funding

This research received no external funding.