, Volume 17, Issue 3, pp 427–435 | Cite as

A novel germline mutation at exon 10 of MEN1 gene: a clinical survey and positive genotype-phenotype analysis of a MEN1 Italian family, including monozygotic twins

  • Andrea Palermo
  • Ettore Capoluongo
  • Rossella Del Toro
  • Silvia Manfrini
  • Paolo Pozzilli
  • Daria Maggi
  • Giuseppe DefeudisEmail author
  • Francesco Pantano
  • Roberto Coppola
  • Francesco Maria Di Matteo
  • Marco Raffaelli
  • Paola Concolino
  • Alberto Falchetti
Case Report



Clinical phenotype variability in MEN1 syndrome exists and evidence for an established genotype-phenotype is lacking. However, a higher aggressiveness of MEN1-associated gastro-entero-pancreatic (GEP) (neuro)endocrine tumours (NETs) tumours has been reported when MEN1 gene truncating mutations are detected. We found a novel germline truncating mutation of MEN1 gene at exon 10 in a subject with an aggressive clinical behavior of GEP-NETs. Successively, other two mutant-affected familial members have been identified.


The aim of this observational study was to investigate genotype-phenotype correlation in these three members, with attention to GPE-NETs behavior over the years.


The genetic and clinical data obtained and the follow-up screening program (2012–2016) were according to the International Guidelines in a multidisciplinary academic reference center. The familial history collected strongly suggested MEN1 GEP-NETs in at least other four members from different generations.


Three MEN1 patients (aged 30–69 years at MEN1 diagnosis) were clinically screened for MEN1 GEP-NETs, both functioning and nonfunctioning.


Biochemical, imaging, and nuclear medicine tests and fine-needle agobiopsy were performed, depending on found/emerging clinical symptoms/biochemical abnormalities, and made when necessary.


Our clinical survey found strong genotype-phenotype correlation with aggressive MEN1 GEP-NETs (G1, G2-NETs, and multiple ZES/gastrinomas) over the years. The familial history strongly suggested ZES/gastrinoma in progenitors from previous generations.


This novel MEN1 truncating mutation correlates with an aggressive evolution and behavior of MEN1 GEP-NETs in studied affected subjects, confirming the need for MEN1 individuals to be evaluated by a skilled multidisciplinary team, as also stated by International Guidelines.


MEN1 MEN1 gene GEP-NETs Genotype-phenotype correlations MEN1 monozygotic twins 



We thank all the patients and their families for participating in this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

42000_2018_44_MOESM1_ESM.docx (25 kb)
ESM 1 (DOCX 25 kb)


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Copyright information

© Hellenic Endocrine Society 2018

Authors and Affiliations

  • Andrea Palermo
    • 1
  • Ettore Capoluongo
    • 2
  • Rossella Del Toro
    • 1
  • Silvia Manfrini
    • 1
  • Paolo Pozzilli
    • 1
  • Daria Maggi
    • 1
  • Giuseppe Defeudis
    • 1
    • 3
    • 4
    Email author
  • Francesco Pantano
    • 5
  • Roberto Coppola
    • 6
  • Francesco Maria Di Matteo
    • 7
  • Marco Raffaelli
    • 8
  • Paola Concolino
    • 2
  • Alberto Falchetti
    • 9
  1. 1.Unit of Endocrinology and Diabetes, Department of MedicineCampus Bio-Medico University of RomeRomeItaly
  2. 2.Laboratory of Molecular Biology, Institute of Biochemistry and Clinical BiochemistryCatholic UniversityRomeItaly
  3. 3.Department of Experimental MedicineSapienza University of RomeRomeItaly
  4. 4.Unit of Endocrinology and Diabetes, Department of MedicineUniversity Campus Bio Medico di RomaRomeItaly
  5. 5.Medical Oncology DepartmentCampus Bio-Medico University of RomeRomeItaly
  6. 6.Department of General SurgeryCampus Bio-Medico University of RomeRomeItaly
  7. 7.Digestive Endoscopy UnitCampus Bio-Medico University of RomeRomeItaly
  8. 8.Unit of Endocrine and Metabolic SurgeryCatholic UniversityRomeItaly
  9. 9.EndOsmet Unit, Villa Donatello Private HospitalFlorence and Villalba HospitalBolognaItaly

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