PMID- 33150274
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240330
IS  - 2472-1972 (Electronic)
IS  - 2472-1972 (Linking)
VI  - 4
IP  - 11
DP  - 2020 Nov 1
TI  - Multiple Endocrine Neoplasia Type 1 (MEN1) Phenocopy Due to a Cell Cycle Division 
      73 (CDC73) Variant.
PG  - bvaa142
LID - 10.1210/jendso/bvaa142 [doi]
LID - bvaa142
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder 
      characterized by the combined occurrence of parathyroid tumors, pituitary 
      adenomas, and pancreatic neuroendocrine neoplasms (PNENs). MEN1 is caused by 
      germline MEN1 mutations in > 75% of patients, and the remaining 25% of patients 
      may have mutations in unidentified genes or represent phenocopies with mutations 
      in genes such as cell cycle division 73 (CDC73), the calcium sensing receptor 
      (CASR), and cyclin-dependent kinase inhibitor 1B (CDKN1B), which are associated 
      with the hyperparathyroidism-jaw tumor syndrome, familial hypocalciuric 
      hypercalcemia type 1, and MEN4, respectively. Here, we report a heterozygous 
      c.1138C>T (p.Leu380Phe) CDC73 germline variant in a clinically diagnosed MEN1 
      patient, based on combined occurrence of primary hyperparathyroidism, acromegaly, 
      and a PNEN. Characterization of the PNEN confirmed it was a neuroendocrine 
      neoplasm as it immuno-stained positively for chromogranin and glucagon. The rare 
      variant p.Leu380Phe occurred in a highly conserved residue, and further analysis 
      using RNA-Scope indicated that it was associated with a significant reduction in 
      CDC73 expression in the PNEN. Previously, CDC73 mutations have been reported to 
      be associated with tumors of the parathyroids, kidneys, uterus, and exocrine 
      pancreas. Thus, our report of a patient with PNEN and somatotrophinoma who had a 
      CDC73 variant, provides further evidence that CDC73 variants may result in a MEN1 
      phenocopy.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the 
      Endocrine Society.
FAU - Lines, Kate E
AU  - Lines KE
AD  - Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of 
      Oxford, Churchill Hospital, Oxford, UK.
FAU - Nachtigall, Lisa B
AU  - Nachtigall LB
AD  - Neuroendocrine Unit, Massachusetts General Hospital/Harvard Medical School, 
      Boston, Massachusetts.
FAU - Dichtel, Laura E
AU  - Dichtel LE
AD  - Neuroendocrine Unit, Massachusetts General Hospital/Harvard Medical School, 
      Boston, Massachusetts.
FAU - Cranston, Treena
AU  - Cranston T
AD  - Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of 
      Oxford, Churchill Hospital, Oxford, UK.
FAU - Boon, Hannah
AU  - Boon H
AD  - Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of 
      Oxford, Churchill Hospital, Oxford, UK.
FAU - Zhang, Xun
AU  - Zhang X
AD  - Neuroendocrine Unit, Massachusetts General Hospital/Harvard Medical School, 
      Boston, Massachusetts.
FAU - Kooblall, Kreepa G
AU  - Kooblall KG
AD  - Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of 
      Oxford, Churchill Hospital, Oxford, UK.
FAU - Stevenson, Mark
AU  - Stevenson M
AD  - Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of 
      Oxford, Churchill Hospital, Oxford, UK.
FAU - Thakker, Rajesh V
AU  - Thakker RV
AD  - Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of 
      Oxford, Churchill Hospital, Oxford, UK.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - K23 DK113220/DK/NIDDK NIH HHS/United States
PT  - Case Reports
DEP - 20200926
PL  - United States
TA  - J Endocr Soc
JT  - Journal of the Endocrine Society
JID - 101697997
PMC - PMC7594654
OTO - NOTNLM
OT  - RNA-Scope
OT  - acromegaly
OT  - pancreatic neuroendocrine neoplasm
OT  - primary hyperparathyroidism
EDAT- 2020/11/06 06:00
MHDA- 2020/11/06 06:01
PMCR- 2020/09/26
CRDT- 2020/11/05 06:09
PHST- 2020/08/21 00:00 [received]
PHST- 2020/09/24 00:00 [accepted]
PHST- 2020/11/05 06:09 [entrez]
PHST- 2020/11/06 06:00 [pubmed]
PHST- 2020/11/06 06:01 [medline]
PHST- 2020/09/26 00:00 [pmc-release]
AID - bvaa142 [pii]
AID - 10.1210/jendso/bvaa142 [doi]
PST - epublish
SO  - J Endocr Soc. 2020 Sep 26;4(11):bvaa142. doi: 10.1210/jendso/bvaa142. eCollection 
      2020 Nov 1.