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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

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Abstract

Context

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.

Objective

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.

Design

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.

Patients

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

Methods

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

Results

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.

Conclusions

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.

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Acknowledgments

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

Author information

Author notes

  1. Andrea Palermo and Ettore Capoluongo contributed equally to this work.

Authors and Affiliations

  1. Unit of Endocrinology and Diabetes, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy

    Andrea Palermo, Rossella Del Toro, Silvia Manfrini, Paolo Pozzilli, Daria Maggi & Giuseppe Defeudis

  2. Laboratory of Molecular Biology, Institute of Biochemistry and Clinical Biochemistry, Catholic University, Rome, Italy

    Ettore Capoluongo & Paola Concolino

  3. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

    Giuseppe Defeudis

  4. Unit of Endocrinology and Diabetes, Department of Medicine, University Campus Bio Medico di Roma, Via Alvaro del Portillo 21, Rome, Italy

    Giuseppe Defeudis

  5. Medical Oncology Department, Campus Bio-Medico University of Rome, Rome, Italy

    Francesco Pantano

  6. Department of General Surgery, Campus Bio-Medico University of Rome, Rome, Italy

    Roberto Coppola

  7. Digestive Endoscopy Unit, Campus Bio-Medico University of Rome, Rome, Italy

    Francesco Maria Di Matteo

  8. Unit of Endocrine and Metabolic Surgery, Catholic University, Rome, Italy

    Marco Raffaelli

  9. EndOsmet Unit, Villa Donatello Private Hospital, Florence and Villalba Hospital, Bologna, Italy

    Alberto Falchetti

Authors
  1. Andrea Palermo
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  2. Ettore Capoluongo
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  3. Rossella Del Toro
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  4. Silvia Manfrini
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  7. Giuseppe Defeudis
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  8. Francesco Pantano
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  9. Roberto Coppola
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  10. Francesco Maria Di Matteo
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  11. Marco Raffaelli
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  12. Paola Concolino
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  13. Alberto Falchetti
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Corresponding author

Correspondence to Giuseppe Defeudis.

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Palermo, A., Capoluongo, E., Del Toro, R. et al. 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. Hormones 17, 427–435 (2018). https://doi.org/10.1007/s42000-018-0044-2

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  • DOI: https://doi.org/10.1007/s42000-018-0044-2

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