PMID- 29497973
OWN - NLM
STAT- MEDLINE
DCOM- 20190211
LR  - 20190215
IS  - 1559-0100 (Electronic)
IS  - 1355-008X (Linking)
VI  - 62
IP  - 1
DP  - 2018 Oct
TI  - Multiple endocrine neoplasia type 1: analysis of germline MEN1 mutations in the 
      Italian multicenter MEN1 patient database.
PG  - 215-233
LID - 10.1007/s12020-018-1566-8 [doi]
AB  - PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is caused by germline 
      inactivating mutations of the MEN1 gene. Currently, no direct genotype-phenotype 
      correlation is identified. We aim to analyze MEN1 mutation site and features, and 
      possible correlations between the mutation type and/or the affected menin 
      functional domain and clinical presentation in patients from the Italian 
      multicenter MEN1 database, one of the largest worldwide MEN1 mutation series 
      published to date. METHODS: The study included the analysis of MEN1 mutation 
      profile in 410 MEN1 patients [370 familial cases from 123 different pedigrees (48 
      still asymptomatic at the time of this study) and 40 single cases]. RESULTS: We 
      identified 99 different mutations: 41 frameshift [small intra-exon deletions (28) 
      or insertions (13)], 13 nonsense, 26 missense and 11 splicing site mutations, 4 
      in-frame small deletions, and 4 intragenic large deletions spanning more than one 
      exon. One family had two different inactivating MEN1 mutations on the same 
      allele. Gastro-entero-pancreatic tumors resulted more frequent in patients with a 
      nonsense mutation, and thoracic neuroendocrine tumors in individuals bearing a 
      splicing-site mutation. CONCLUSIONS: Our data regarding mutation type frequency 
      and distribution are in accordance with previously published data: MEN1 mutations 
      are scattered through the entire coding region, and truncating mutations are the 
      most common in MEN1 syndrome. A specific direct correlation between MEN1 genotype 
      and clinical phenotype was not found in all our families, and wide intra-familial 
      clinical variability and variable disease penetrance were both confirmed, 
      suggesting a role for modifying, still undetermined, factors, explaining the 
      variable MEN1 tumorigenesis.
FAU - Marini, Francesca
AU  - Marini F
AD  - Department of Surgery and Translational Medicine, University of Florence, 
      Florence, Italy.
FAU - Giusti, Francesca
AU  - Giusti F
AD  - Department of Surgery and Translational Medicine, University of Florence, 
      Florence, Italy.
FAU - Fossi, Caterina
AU  - Fossi C
AD  - Department of Surgery and Translational Medicine, University of Florence, 
      Florence, Italy.
FAU - Cioppi, Federica
AU  - Cioppi F
AD  - Department of Surgery and Translational Medicine, University of Florence, 
      Florence, Italy.
FAU - Cianferotti, Luisella
AU  - Cianferotti L
AD  - Department of Surgery and Translational Medicine, University of Florence, 
      Florence, Italy.
FAU - Masi, Laura
AU  - Masi L
AD  - Department of Surgery and Translational Medicine, University of Florence, 
      Florence, Italy.
FAU - Boaretto, Francesca
AU  - Boaretto F
AD  - Familial Cancer Clinic, Veneto Institute of Oncology IRCCS, Padua, Italy.
FAU - Zovato, Stefania
AU  - Zovato S
AD  - Familial Cancer Clinic, Veneto Institute of Oncology IRCCS, Padua, Italy.
FAU - Cetani, Filomena
AU  - Cetani F
AD  - Department of Clinical and Experimental Medicine, Section of Endocrinology, 
      University of Pisa, Pisa, Italy.
FAU - Colao, Annamaria
AU  - Colao A
AD  - Endocrinology Unit, Department of Clinical Medicine and Surgery, University of 
      Naples Federico II, Naples, Italy.
FAU - Davi, Maria Vittoria
AU  - Davi MV
AD  - Internal Medicine, Section of Endocrinology, Department of Medicine, University 
      of Verona, Verona, Italy.
FAU - Faggiano, Antongiulio
AU  - Faggiano A
AD  - Endocrinology Unit, Department of Clinical Medicine and Surgery, University of 
      Naples Federico II, Naples, Italy.
FAU - Fanciulli, Giuseppe
AU  - Fanciulli G
AD  - NET Unit, Department of Clinical and Experimental Medicine, University of 
      Sassari, Sassari, Italy.
FAU - Ferolla, Piero
AU  - Ferolla P
AD  - Multidisciplinar NET Center, Umbria Regional Cancer Network, Azienda Ospedaliera 
      di Perugia and University of Perugia, Perugia, Italy.
FAU - Ferone, Diego
AU  - Ferone D
AD  - Endocrinology Unit, Department of Internal Medicine and Medical Specialties 
      (DiMI), Policlinico San Martino, University of Genoa, Genoa, Italy.
FAU - Loli, Paola
AU  - Loli P
AD  - Department of Endocrinology, Hospital Niguarda Ca' Granda, Milan, Italy.
FAU - Mantero, Franco
AU  - Mantero F
AD  - Division of Endocrinology, Department of Medicine (DIMED), University of Padua, 
      Padua, Italy.
FAU - Marcocci, Claudio
AU  - Marcocci C
AD  - Department of Clinical and Experimental Medicine, Section of Endocrinology, 
      University of Pisa, Pisa, Italy.
FAU - Opocher, Giuseppe
AU  - Opocher G
AD  - Familial Cancer Clinic, Veneto Institute of Oncology IRCCS, Padua, Italy.
FAU - Beck-Peccoz, Paolo
AU  - Beck-Peccoz P
AD  - University of Milan, Milan, Italy.
FAU - Persani, Luca
AU  - Persani L
AD  - Department of Clinical Sciences and Community Health, University of Milan, Milan, 
      Italy.
AD  - Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, 
      Milan, Italy.
FAU - Scillitani, Alfredo
AU  - Scillitani A
AD  - Unit of Endocrinology 'Casa Sollievo della Sofferenza' Hospital, IRCCS, San 
      Giovanni Rotondo, Foggia, Italy.
FAU - Guizzardi, Fabiana
AU  - Guizzardi F
AD  - Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, 
      Milan, Italy.
FAU - Spada, Anna
AU  - Spada A
AD  - Department of Clinical Sciences and Community Health, University of Milan, Milan, 
      Italy.
FAU - Tomassetti, Paola
AU  - Tomassetti P
AD  - Department of Medical and Surgical Sciences, S. Orsola-Malpighi University 
      Hospital, Bologna, Italy.
FAU - Tonelli, Francesco
AU  - Tonelli F
AD  - Department of Surgery and Translational Medicine, University of Florence, 
      Florence, Italy.
FAU - Brandi, Maria Luisa
AU  - Brandi ML
AUID- ORCID: 0000-0002-8741-0592
AD  - Department of Surgery and Translational Medicine, University of Florence, 
      Florence, Italy. marialuisa.brandi@unifi.it.
LA  - eng
GR  - 2014/0431/Ente Cassa di Risparmio di Firenze/International
PT  - Journal Article
DEP - 20180301
PL  - United States
TA  - Endocrine
JT  - Endocrine
JID - 9434444
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
EIN - Endocrine. 2018 Jul 21;:. PMID: 30032405
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Child
MH  - Child, Preschool
MH  - Databases, Factual
MH  - Female
MH  - Genotype
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Italy
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Phenotype
MH  - Proto-Oncogene Proteins/*genetics
MH  - Young Adult
OTO - NOTNLM
OT  - Genetic test
OT  - Genotype-phenotype correlation
OT  - MEN1 inactivating mutations
OT  - Multiple endocrine neoplasia type 1
EDAT- 2018/03/03 06:00
MHDA- 2019/02/12 06:00
CRDT- 2018/03/03 06:00
PHST- 2017/11/28 00:00 [received]
PHST- 2018/02/08 00:00 [accepted]
PHST- 2018/03/03 06:00 [pubmed]
PHST- 2019/02/12 06:00 [medline]
PHST- 2018/03/03 06:00 [entrez]
AID - 10.1007/s12020-018-1566-8 [pii]
AID - 10.1007/s12020-018-1566-8 [doi]
PST - ppublish
SO  - Endocrine. 2018 Oct;62(1):215-233. doi: 10.1007/s12020-018-1566-8. Epub 2018 Mar 
      1.