PMID- 32396602
OWN - NLM
STAT- MEDLINE
DCOM- 20210203
LR  - 20210203
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 105
IP  - 7
DP  - 2020 Jul 1
TI  - Clues For Genetic Anticipation In Multiple Endocrine Neoplasia Type 1.
LID - dgaa257 [pii]
LID - 10.1210/clinem/dgaa257 [doi]
AB  - CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant 
      hereditary disease caused by the loss of function of the MEN1 gene, a 
      tumor-suppressor gene that encodes the protein menin. It is characterized by the 
      occurrence of primary hyperparathyroidism (pHPT), duodenopancreatic 
      neuroendocrine tumors (dpNET), pituitary tumors (PIT), adrenal adenomas, and 
      bronchopulmonary (bp-NET), thymic, and gastric neuroendocrine tumors. More 
      insight into factors influencing the age-related penetrance of MEN1 
      manifestations could provide clues for more personalized screening programs. 
      OBJECTIVE: To investigate whether genetic anticipation plays a role in the 
      largest known MEN1 families in the Netherlands. METHODS: All Dutch MEN1 families 
      with >/= 10 affected members in >/= 2 successive generations were identified. Age at 
      detection of the different MEN1-related manifestations were compared among 
      generations using regression analyses adjusted for competing risks. To correct 
      for the beneficial effect of being under surveillance, manifestations occurring 
      during surveillance were also separately compared. RESULTS: A total of 152 MEN1 
      patients from 10 families were included. A significantly decreased age at 
      detection of pHPT, dpNET, PIT, and bp-NET was found in successive generations 
      (P < 0.0001). Adjusted analyses led to the same results. CONCLUSIONS: These 
      results suggest the presence of genetic anticipation. However, due to a risk of 
      residual bias, the results must be interpreted with caution. After independent 
      validation in other cohorts and further translational research investigating the 
      molecular mechanisms explaining this phenomenon in MEN1, the results might add to 
      future, more personalized, screening protocols and earlier screening for future 
      generations of MEN1 patients.
CI  - (c) Endocrine Society 2020. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - van den Broek, Medard F M
AU  - van den Broek MFM
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - van Nesselrooij, Bernadette P M
AU  - van Nesselrooij BPM
AD  - Department of Medical Genetics, Wilhelmina Children's Hospital, University 
      Medical Center Utrecht, Utrecht, The Netherlands.
FAU - Pieterman, Carolina R C
AU  - Pieterman CRC
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - Verrijn Stuart, Annemarie A
AU  - Verrijn Stuart AA
AD  - Department of Pediatric Endocrinology, Wilhelmina Children's Hospital, University 
      Medical Center Utrecht, Utrecht, The Netherlands.
FAU - van de Ven, Annenienke C
AU  - van de Ven AC
AD  - Department of Endocrinology, Radboud University Medical Center, Nijmegen, The 
      Netherlands.
FAU - de Herder, Wouter W
AU  - de Herder WW
AD  - Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The 
      Netherlands.
FAU - Dekkers, Olaf M
AU  - Dekkers OM
AD  - Departments of Endocrinology and Metabolism and Clinical Epidemiology, Leiden 
      University Medical Center, Leiden, The Netherlands.
FAU - Drent, Madeleine L
AU  - Drent ML
AD  - Department of Internal Medicine, Section of Endocrinology, Amsterdam UMC, 
      location VU University Medical Center, Amsterdam, The Netherlands.
FAU - Havekes, Bas
AU  - Havekes B
AD  - Department of Internal Medicine, Division of Endocrinology, Maastricht University 
      Medical Center, Maastricht, The Netherlands.
FAU - Kerstens, Michiel N
AU  - Kerstens MN
AD  - Department of Endocrinology, University Medical Center Groningen, Groningen, The 
      Netherlands.
FAU - Bisschop, Peter H
AU  - Bisschop PH
AD  - Department of Endocrinology and Metabolism, Amsterdam UMC, location Academic 
      Medical Center, Amsterdam, The Netherlands.
FAU - Valk, Gerlof D
AU  - Valk GD
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Aged, 80 and over
MH  - *Anticipation, Genetic
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Mutation
MH  - Netherlands
MH  - Proto-Oncogene Proteins/genetics
MH  - Young Adult
OTO - NOTNLM
OT  - age of onset
OT  - genetic anticipation
OT  - multiple endocrine neoplasia type 1
OT  - surveillance
EDAT- 2020/05/13 06:00
MHDA- 2021/02/04 06:00
CRDT- 2020/05/13 06:00
PHST- 2020/02/24 00:00 [received]
PHST- 2020/05/08 00:00 [accepted]
PHST- 2020/05/13 06:00 [pubmed]
PHST- 2021/02/04 06:00 [medline]
PHST- 2020/05/13 06:00 [entrez]
AID - 5836321 [pii]
AID - 10.1210/clinem/dgaa257 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2020 Jul 1;105(7):dgaa257. doi: 10.1210/clinem/dgaa257.