PMID- 38294658
OWN - NLM
STAT- Publisher
LR  - 20240131
IS  - 1720-8386 (Electronic)
IS  - 0391-4097 (Linking)
DP  - 2024 Jan 31
TI  - A novel likely pathogenetic variant p.(Cys235Arg) of the MEN1 gene in multiple 
      endocrine neoplasia type 1 with multifocal glucagonomas.
LID - 10.1007/s40618-023-02287-x [doi]
AB  - PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine 
      syndrome caused by pathogenic variants in MEN1 tumor suppressor gene. Diagnosis 
      is commonly based on clinical criteria and confirmed by genetic testing. The 
      objective of the present study was to report on a MEN1 case characterized by 
      multiple pancreatic glucagonomas, with particular concern on the possible 
      predisposing genetic defects. METHODS: While conducting an extensive review of 
      the most recent scientific evidence on the unusual glucagonoma familial forms, we 
      analyzed the MEN1 gene in a 35-year-old female with MEN1, as well as her son and 
      daughter, using Sanger and next-generation sequencing (NGS) approaches. We 
      additionally explored the functional and structural consequences of the 
      identified variant using in silico analyses. RESULTS: NGS did not show any known 
      pathogenic variant in the tested regions. However, a new non-conservative variant 
      in exon 4 of MEN1 gene was found in heterozygosity in the patient and in her 
      daughter, resulting in an amino acid substitution from hydrophobic cysteine to 
      hydrophilic arginine at c.703T > C, p.(Cys235Arg). This variant is absent from 
      populations databases and was never reported in full papers: its characteristics, 
      together with the high specificity of the patient's clinical phenotype, pointed 
      toward a possible causative role. CONCLUSION: Our findings confirm the need for 
      careful genetic analysis of patients with MEN1 and establish a likely pathogenic 
      role for the new p.(Cys235Arg) variant, at least in the rare subset of MEN1 
      associated with glucagonomas.
CI  - (c) 2024. The Author(s).
FAU - Smirne, C
AU  - Smirne C
AUID- ORCID: 0000-0002-3338-5416
AD  - Department of Translational Medicine, University of Piemonte Orientale, Via 
      Solaroli 17, 28100, Novara, Italy. carlo.smirne@med.uniupo.it.
AD  - Division of Internal Medicine, University Hospital Maggiore della Carita, 28100, 
      Novara, Italy. carlo.smirne@med.uniupo.it.
FAU - Giacomini, G M
AU  - Giacomini GM
AUID- ORCID: 0000-0001-5972-4626
AD  - Department of Translational Medicine, University of Piemonte Orientale, Via 
      Solaroli 17, 28100, Novara, Italy.
AD  - Division of Internal Medicine, University Hospital Maggiore della Carita, 28100, 
      Novara, Italy.
FAU - Berton, A M
AU  - Berton AM
AUID- ORCID: 0000-0002-4745-2624
AD  - Division of Endocrinology, Diabetes and Metabolism, City of Health and Science 
      University Hospital, 10126, Turin, Italy.
FAU - Pasini, B
AU  - Pasini B
AUID- ORCID: 0000-0002-4373-1212
AD  - Department of Medical Sciences, University of Turin, 10126, Turin, Italy.
AD  - Division of Medical Genetics, City of Health and Science University Hospital, 
      10126, Turin, Italy.
FAU - Mercalli, F
AU  - Mercalli F
AUID- ORCID: 0000-0003-0818-4660
AD  - Division of Pathology, University Hospital Maggiore della Carita, 28100, Novara, 
      Italy.
FAU - Prodam, F
AU  - Prodam F
AUID- ORCID: 0000-0001-9660-5335
AD  - Department of Health Sciences, University of Piemonte Orientale, 28100, Novara, 
      Italy.
AD  - Division of Endocrinology, University Hospital Maggiore della Carita, 28100, 
      Novara, Italy.
FAU - Caputo, M
AU  - Caputo M
AUID- ORCID: 0000-0003-0470-9343
AD  - Department of Health Sciences, University of Piemonte Orientale, 28100, Novara, 
      Italy.
AD  - Division of Endocrinology, University Hospital Maggiore della Carita, 28100, 
      Novara, Italy.
FAU - Brosens, L A A
AU  - Brosens LAA
AUID- ORCID: 0000-0003-1341-8994
AD  - Department of Pathology, University Medical Center Utrecht, 3584 CX, Utrecht, The 
      Netherlands.
FAU - Mollero, E L M
AU  - Mollero ELM
AUID- ORCID: 0000-0002-1903-5874
AD  - Division of Endocrinology, University Hospital Maggiore della Carita, 28100, 
      Novara, Italy.
FAU - Pitino, R
AU  - Pitino R
AUID- ORCID: 0000-0002-2685-3090
AD  - Division of Endocrinology, University Hospital Maggiore della Carita, 28100, 
      Novara, Italy.
FAU - Pirisi, M
AU  - Pirisi M
AUID- ORCID: 0000-0001-9740-0155
AD  - Department of Translational Medicine, University of Piemonte Orientale, Via 
      Solaroli 17, 28100, Novara, Italy.
AD  - Division of Internal Medicine, University Hospital Maggiore della Carita, 28100, 
      Novara, Italy.
FAU - Aimaretti, G
AU  - Aimaretti G
AUID- ORCID: 0000-0002-6186-0106
AD  - Department of Translational Medicine, University of Piemonte Orientale, Via 
      Solaroli 17, 28100, Novara, Italy.
AD  - Division of Endocrinology, University Hospital Maggiore della Carita, 28100, 
      Novara, Italy.
FAU - Ghigo, E
AU  - Ghigo E
AUID- ORCID: 0000-0002-2809-8105
AD  - Division of Endocrinology, Diabetes and Metabolism, City of Health and Science 
      University Hospital, 10126, Turin, Italy.
AD  - Department of Medical Sciences, University of Turin, 10126, Turin, Italy.
LA  - eng
PT  - Journal Article
DEP - 20240131
PL  - Italy
TA  - J Endocrinol Invest
JT  - Journal of endocrinological investigation
JID - 7806594
SB  - IM
OTO - NOTNLM
OT  - Adrenal gland adenoma
OT  - Familiar
OT  - Necrolytic migratory erythema
OT  - Neuroendocrine pancreatic tumor
OT  - Next-generation sequencing
OT  - Primary hyperparathyroidism
EDAT- 2024/01/31 12:42
MHDA- 2024/01/31 12:42
CRDT- 2024/01/31 11:16
PHST- 2023/06/26 00:00 [received]
PHST- 2023/12/17 00:00 [accepted]
PHST- 2024/01/31 12:42 [medline]
PHST- 2024/01/31 12:42 [pubmed]
PHST- 2024/01/31 11:16 [entrez]
AID - 10.1007/s40618-023-02287-x [pii]
AID - 10.1007/s40618-023-02287-x [doi]
PST - aheadofprint
SO  - J Endocrinol Invest. 2024 Jan 31. doi: 10.1007/s40618-023-02287-x.