MEN4, the MEN1 Mimicker: A Case Series of three Phenotypically Heterogenous Patients With Unique CDKN1B Mutations.
CDKN1B germline mutation
MEN4
atypical carcinoid tumor
multiple endocrine neoplasia type 4
pancreatic neuroendocrine tumor
pituitary adenoma
primary hyperparathyroidism
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
14 07 2022
14 07 2022
Historique:
received:
30
09
2021
pubmed:
25
3
2022
medline:
19
7
2022
entrez:
24
3
2022
Statut:
ppublish
Résumé
Germline CDKN1B pathogenic variants result in multiple endocrine neoplasia type 4 (MEN4), an autosomal dominant hereditary tumor syndrome variably associated with primary hyperparathyroidism, pituitary adenoma, and duodenopancreatic neuroendocrine tumors. To report the phenotype of 3 unrelated cases each with a unique germline CDKN1B variant (of which 2 are novel) and compare these cases with those described in the current literature. Three case studies, including clinical presentation, germline, and tumor genetic analysis and family history. Two tertiary University Hospitals in Sydney, New South Wales, and 1 tertiary University Hospital in Canberra, Australian Capital Territory, Australia. Phenotype of the 3 cases and their kindred; molecular analysis and tumor p27kip1 immunohistochemistry. Family A: The proband developed multiglandular primary hyperparathyroidism, a microprolactinoma and a multifocal nonfunctioning duodenopancreatic neuroendocrine tumor. Family B: The proband was diagnosed with primary hyperparathyroidism from a single parathyroid adenoma. Family C: The proband was diagnosed with a nonfunctioning pituitary microadenoma and ectopic Cushing's syndrome from an atypical thymic carcinoid tumor. Germline sequencing in each patient identified a unique variant in CDKN1B, 2 of which are novel (c.179G > A, p.Trp60*; c.475G > A, p.Asp159Asn) and 1 previously reported (c.374_375delCT, p.Ser125*). Germline CDKN1B pathogenic variants cause the syndrome MEN4. The phenotype resulting from the 3 pathogenic variants described in this series highlights the heterogenous nature of this syndrome, ranging from isolated primary hyperparathyroidism to the full spectrum of endocrine manifestations. We report the first described cases of a prolactinoma and an atypical thymic carcinoid tumor in MEN4.
Identifiants
pubmed: 35323929
pii: 6552252
doi: 10.1210/clinem/dgac162
pmc: PMC9282358
doi:
Substances chimiques
CDKN1B protein, human
0
Cyclin-Dependent Kinase Inhibitor p27
147604-94-2
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2339-2349Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.
Références
Nucleic Acids Res. 2019 Jan 8;47(D1):D941-D947
pubmed: 30371878
J Clin Endocrinol Metab. 2020 Jun 1;105(6):
pubmed: 32232325
Oncogene. 2000 Apr 6;19(15):1875-84
pubmed: 10773877
J Bone Miner Res. 2021 Jan;36(1):100-109
pubmed: 32780883
J Clin Endocrinol Metab. 2009 May;94(5):1826-34
pubmed: 19141585
Fam Cancer. 2020 Apr;19(2):189-192
pubmed: 32052251
Cancer Res. 2002 Jun 1;62(11):3048-51
pubmed: 12036912
Endocr Relat Cancer. 2017 Oct;24(10):T195-T208
pubmed: 28824003
Endocr Relat Cancer. 2012 May 03;19(3):233-41
pubmed: 22291433
Hum Mutat. 2011 May;32(5):557-63
pubmed: 21520333
J Clin Endocrinol Metab. 2012 Sep;97(9):2990-3011
pubmed: 22723327
Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15558-63
pubmed: 17030811
Science. 2011 Mar 4;331(6021):1199-203
pubmed: 21252315
Neuroendocrinology. 2021;111(7):609-630
pubmed: 32971521
Hum Mutat. 2016 Jun;37(6):564-9
pubmed: 26931183
J Clin Endocrinol Metab. 2019 Mar 1;104(3):753-764
pubmed: 30339208
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
Nat Commun. 2018 Oct 12;9(1):4158
pubmed: 30315258
Nucleic Acids Res. 2016 Jan 4;44(D1):D7-19
pubmed: 26615191
J Clin Endocrinol Metab. 2003 Mar;88(3):1066-81
pubmed: 12629087
Mol Cell Endocrinol. 2014 Apr 5;386(1-2):2-15
pubmed: 23933118
Nature. 1998 Nov 12;396(6707):177-80
pubmed: 9823898
Cell. 1994 Jul 15;78(1):59-66
pubmed: 8033212
Clin Endocrinol (Oxf). 2012 May;76(5):719-24
pubmed: 22026581
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Adv Med Biol. 2017 1st Quarter;118:83-122
pubmed: 28680740
Endocr Rev. 2021 Mar 15;42(2):133-170
pubmed: 33249439
Curr Protoc Bioinformatics. 2012 Sep;Chapter 1:Unit1.13
pubmed: 22948725
Front Horm Res. 2013;41:63-78
pubmed: 23652671
J Clin Endocrinol Metab. 2005 May;90(5):2603-9
pubmed: 15713725
Endocr Connect. 2014 Nov 21;4(1):1-8
pubmed: 25416039
Endocrine. 2022 Jan;75(1):23-32
pubmed: 34773560
Endocrine. 2015 May;49(1):58-64
pubmed: 25645465
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
J Clin Endocrinol Metab. 2019 Sep 1;104(9):3637-3646
pubmed: 30990521
Br J Cancer. 2000 Oct;83(8):1003-8
pubmed: 10993646
Genes Dev. 1994 Jan;8(1):9-22
pubmed: 8288131
Clin Endocrinol (Oxf). 2000 Aug;53(2):205-11
pubmed: 10931102
Hum Mutat. 2010 Jan;31(1):E1089-101
pubmed: 19953642
Nature. 2012 Jan 29;482(7384):226-31
pubmed: 22286061
Nat Commun. 2015 Jan 21;6:6140
pubmed: 25608029
J Bone Miner Res. 2009 Aug;24(8):1404-10
pubmed: 19309299
Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5291-5
pubmed: 8202483
Endocr Rev. 2013 Apr;34(2):239-77
pubmed: 23371967
J Clin Endocrinol Metab. 2007 Aug;92(8):3321-5
pubmed: 17519308
Case Rep Endocrinol. 2015;2015:510985
pubmed: 26257968
Hum Mutat. 2010 Nov;31(11):E1825-35
pubmed: 20824794
J Intern Med. 2009 Jul;266(1):1-4
pubmed: 19522821
PLoS Genet. 2013 Mar;9(3):e1003350
pubmed: 23555276
Nucleic Acids Res. 2018 Jan 4;46(D1):D1062-D1067
pubmed: 29165669
Nature. 1996 Jul 25;382(6589):325-31
pubmed: 8684460
Eur J Endocrinol. 2014 Aug;171(2):K7-K17
pubmed: 24819502
Eur J Endocrinol. 2017 May;176(5):635-644
pubmed: 28220018
Nat Rev Cancer. 2008 Apr;8(4):253-67
pubmed: 18354415