PMID- 33312161
OWN - NLM
STAT- MEDLINE
DCOM- 20210603
LR  - 20210603
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 11
DP  - 2020
TI  - Phenotypes Associated With MEN1 Syndrome: A Focus on Genotype-Phenotype 
      Correlations.
PG  - 591501
LID - 10.3389/fendo.2020.591501 [doi]
LID - 591501
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant inherited 
      tumor syndrome, associated with parathyroid, pituitary, and 
      gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs). MEN1 is usually 
      consequent to different germline and somatic mutations of the MEN1 tumor 
      suppressor gene, although phenocopies have also been reported. This review 
      analyzed main biomedical databases searching for reports on MEN1 gene mutations 
      and focused on aggressive and aberrant clinical manifestations to investigate the 
      potential genotype-phenotype correlation. Despite efforts made by several groups, 
      this link remains elusive to date and evidence that aggressive or aberrant 
      clinical phenotypes may be related to specific mutations has been provided by 
      case reports and small groups of MEN1 patients or families. In such context, a 
      higher risk of aggressive tumor phenotypes has been described in relation to 
      frameshift and non-sense mutations, and predominantly associated with aggressive 
      GEP NETs, particularly pancreatic NETs. In our experience a novel heterozygous 
      missense mutation at c.836C>A in exon 6 was noticed in a MEN1 patient operated 
      for macro-prolactinoma, who progressively developed recurrent parathyroid 
      adenomas, expanding gastrinomas and, long after the first MEN1 manifestation, a 
      neuroendocrine uterine carcinoma. In conclusion, proof of genotype-phenotype 
      correlation is limited but current evidence hints at the need for long-term 
      interdisciplinary surveillance in patients with aggressive phenotypes and 
      genetically confirmed MEN1.
CI  - Copyright (c) 2020 Mele, Mencarelli, Caputo, Mai, Pagano, Aimaretti, Scacchi, 
      Falchetti and Marzullo.
FAU - Mele, Chiara
AU  - Mele C
AD  - Department of Translational Medicine, University of Piemonte Orientale, Novara, 
      Italy.
AD  - Istituto Auxologico Italiano, IRCCS, Division of General Medicine, S. Giuseppe 
      Hospital, Piancavallo, Italy.
FAU - Mencarelli, Monica
AU  - Mencarelli M
AD  - Istituto Auxologico Italiano, IRCCS, Laboratory of Molecular Biology, S. Giuseppe 
      Hospital, Piancavallo, Italy.
FAU - Caputo, Marina
AU  - Caputo M
AD  - Department of Health Sciences, University of Piemonte Orientale, Novara, Italy.
AD  - Division of Endocrinology, University Hospital "Maggiore della Carita", Novara, 
      Italy.
FAU - Mai, Stefania
AU  - Mai S
AD  - Istituto Auxologico Italiano, IRCCS, Laboratory of Metabolic Research, S. 
      Giuseppe Hospital, Piancavallo, Italy.
FAU - Pagano, Loredana
AU  - Pagano L
AD  - Division of Endocrinology, Diabetology and Metabolism, Department of Medical 
      Sciences, University of Turin, Turin, Italy.
FAU - Aimaretti, Gianluca
AU  - Aimaretti G
AD  - Department of Translational Medicine, University of Piemonte Orientale, Novara, 
      Italy.
AD  - Division of Endocrinology, University Hospital "Maggiore della Carita", Novara, 
      Italy.
FAU - Scacchi, Massimo
AU  - Scacchi M
AD  - Istituto Auxologico Italiano, IRCCS, Division of General Medicine, S. Giuseppe 
      Hospital, Piancavallo, Italy.
FAU - Falchetti, Alberto
AU  - Falchetti A
AD  - Istituto Auxologico Italiano, IRCCS, Rehabilitation Unit, S. Giuseppe Hospital, 
      Unit for Bone Metabolism Diseases, Verbania, Italy.
AD  - Diabetes & Lab of Endocrine and Metabolic Research, Dept. of Clinical Sciences & 
      Community Health, University of Milan, Milan, Italy.
FAU - Marzullo, Paolo
AU  - Marzullo P
AD  - Department of Translational Medicine, University of Piemonte Orientale, Novara, 
      Italy.
AD  - Istituto Auxologico Italiano, IRCCS, Division of General Medicine, S. Giuseppe 
      Hospital, Piancavallo, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20201118
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Genetic Association Studies/*methods
MH  - Humans
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/*pathology
MH  - *Mutation
MH  - Proto-Oncogene Proteins/*genetics
PMC - PMC7708377
OTO - NOTNLM
OT  - MEN1
OT  - genotype
OT  - mutations
OT  - phenotype
OT  - tumors
EDAT- 2020/12/15 06:00
MHDA- 2021/06/04 06:00
PMCR- 2020/01/01
CRDT- 2020/12/14 10:56
PHST- 2020/08/04 00:00 [received]
PHST- 2020/10/16 00:00 [accepted]
PHST- 2020/12/14 10:56 [entrez]
PHST- 2020/12/15 06:00 [pubmed]
PHST- 2021/06/04 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2020.591501 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2020 Nov 18;11:591501. doi: 
      10.3389/fendo.2020.591501. eCollection 2020.