Multiple endocrine neoplasia type 2 kindred with novel tandem RET mutations: Case report with an applied in silico mutational tolerance analysis

Rohan Joshi, Thomas E. Heineman, David I. Kutler, Marc A. Cohen, William I. Kuhel

Research output: Contribution to journalArticle

Abstract

Background The American Thyroid Association (ATA) has established guidelines for prophylactic thyroidectomy in multiple endocrine neoplasia type 2A (MEN2A) based on rearranged during transfection (RET) mutations. In silico analysis, which uses computer modeling to predict alterations in protein structure, is a new method for studying these mutations. Methods We describe a kindred with MEN2A, all sharing a well-documented RET mutation, p.C634Y, as well as a mutation of undetermined significance, p.I852M, which we analyzed via in silico analysis. Results The p.C634Y mutation resulted in severe predicted RET alterations, whereas the p.I852M resulted in only modest changes. Both mutations together resulted in only a small additional disruptive effect in protein structure beyond that which occurred with p.C634Y alone. Conclusion Although in silico analysis may be helpful in quantitating changes in protein structure that occur in patients who have novel RET mutations (single or multiple), additional factors must account for the highly variable aggressiveness of the disease (C-cell hyperplasia/medullary thyroid carcinoma [MTC]) noted in our kindred.

Original languageEnglish (US)
Pages (from-to)E1881-E1885
JournalHead and Neck
Volume38
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

Keywords

  • goiter
  • medullary
  • multiple endocrine neoplasia (MEN)
  • parathyroid
  • thyroidectomy

ASJC Scopus subject areas

  • Otorhinolaryngology

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