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Eur J Endocrinol. 2018 Nov 1. pii: EJE-18-0778.R1. doi: 10.1530/EJE-18-0778. [Epub ahead of print]

Germline and somatic mosaicism in a family with Multiple Endocrine Neoplasia type 1 (MEN1) syndrome.

Author information

1
H Beijers, Internal Medicine, Maasziekenhuis Pantein, Boxmeer, 5830 AB, Netherlands.
2
N Stikkelbroeck, Department of Medicine, Division of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
3
A Mensenkamp, Human Genetics, Radboudumc, Nijmegen, Netherlands.
4
R Pfundt, Human Genetics, Radboudumc, Nijmegen, Netherlands.
5
R van der Luijt, Medical Genetics, University Medical Center Utrecht, Utrecht, United Kingdom of Great Britain and Northern Ireland.
6
H Timmers, Department of Medicine, Division of Vascular Medicine, Radboud university medical centre, Nijmegen, Netherlands.
7
A Hermus, Endocrinology, University Medical Center St Radboud, Nijmegen, Netherlands.
8
M Kempers, Human Genetics, Radboudumc, Nijmegen, Netherlands.

Abstract

CONTEXT:

Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the tumor suppressor gene MEN1 and can be diagnosed based on clinical, familial and/or genetic criteria. We present a family in which we found both germline and somatic mosaicism for MEN1. Family description: In our proband we diagnosed MEN1. The mutation was not detected in her parents (DNA extracted from leucocytes). When her brother was found to harbor the same MEN1 mutation as our proband and, around the same time, their father was diagnosed with a neuroendocrine carcinoma, this tumour was investigated for the MEN1 mutation as well. In the histologic biopsy of this tumour the same MEN1 mutation was detected as previously found in his children. Re-analysis of his blood using multiplex ligation-dependent probe amplification (MLPA) showed a minimal, but consistently decreased signal for the MEN1 specific MLPA-probes. The deletion was confirmed in his son by high resolution array analysis. Based on the array data we concluded that the deletion was limited to the MEN1 gene and that the father had both germline and somatic mosaicism for MEN1.

CONCLUSIONS:

To our knowledge this is the first reported family with combined germline and somatic mosaicism for MEN1. This study illustrates that germline mosaicism is important to consider in apparently sporadic de novo MEN1 mutations, because of its particular importance for genetic counseling, specifically when evaluating the risk for family members and when considering the possibility of somatic mosaicism in the parent with germline mosaicism.

PMID:
30481156
DOI:
10.1530/EJE-18-0778

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