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

Fingerprint

Multiple Endocrine Neoplasia Type 2a
Computer Simulation
Transfection
Mutation
Proteins
Thyroidectomy
Hyperplasia
Guidelines

Keywords

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

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Multiple endocrine neoplasia type 2 kindred with novel tandem RET mutations : Case report with an applied in silico mutational tolerance analysis. / Joshi, Rohan; Heineman, Thomas E.; Kutler, David I.; Cohen, Marc A.; Kuhel, William I.

In: Head and Neck, Vol. 38, 01.04.2016, p. E1881-E1885.

Research output: Contribution to journalArticle

Joshi, Rohan ; Heineman, Thomas E. ; Kutler, David I. ; Cohen, Marc A. ; Kuhel, William I. / Multiple endocrine neoplasia type 2 kindred with novel tandem RET mutations : Case report with an applied in silico mutational tolerance analysis. In: Head and Neck. 2016 ; Vol. 38. pp. E1881-E1885.
@article{1b95bc8a5610479db7fad0c256ad2157,
title = "Multiple endocrine neoplasia type 2 kindred with novel tandem RET mutations: Case report with an applied in silico mutational tolerance analysis",
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.",
keywords = "goiter, medullary, multiple endocrine neoplasia (MEN), parathyroid, thyroidectomy",
author = "Rohan Joshi and Heineman, {Thomas E.} and Kutler, {David I.} and Cohen, {Marc A.} and Kuhel, {William I.}",
year = "2016",
month = "4",
day = "1",
doi = "10.1002/hed.24340",
language = "English (US)",
volume = "38",
pages = "E1881--E1885",
journal = "Head and Neck Surgery",
issn = "1043-3074",
publisher = "Wiley-Liss Inc.",

}

TY - JOUR

T1 - Multiple endocrine neoplasia type 2 kindred with novel tandem RET mutations

T2 - Case report with an applied in silico mutational tolerance analysis

AU - Joshi, Rohan

AU - Heineman, Thomas E.

AU - Kutler, David I.

AU - Cohen, Marc A.

AU - Kuhel, William I.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

KW - goiter

KW - medullary

KW - multiple endocrine neoplasia (MEN)

KW - parathyroid

KW - thyroidectomy

UR - http://www.scopus.com/inward/record.url?scp=84959036248&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959036248&partnerID=8YFLogxK

U2 - 10.1002/hed.24340

DO - 10.1002/hed.24340

M3 - Article

VL - 38

SP - E1881-E1885

JO - Head and Neck Surgery

JF - Head and Neck Surgery

SN - 1043-3074

ER -