PMID- 30481156
OWN - NLM
STAT- MEDLINE
DCOM- 20190227
LR  - 20190405
IS  - 1479-683X (Electronic)
IS  - 0804-4643 (Linking)
VI  - 180
IP  - 2
DP  - 2019 Feb 1
TI  - Germline and somatic mosaicism in a family with multiple endocrine neoplasia type 
      1 (MEN1) syndrome.
PG  - K15-K19
LID - EJE-18-0778 [pii]
LID - 10.1530/EJE-18-0778 [doi]
AB  - 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 tumor was investigated for the 
      MEN1 mutation as well. In the histologic biopsy of this tumor, 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.
FAU - Beijers, Hanneke J B H
AU  - Beijers HJBH
AD  - Department of Internal Medicine, Maasziekenhuis Pantein, Boxmeer, The 
      Netherlands.
AD  - Division of Endocrinology, Department of Internal Medicine.
FAU - Stikkelbroeck, Nike M L
AU  - Stikkelbroeck NML
AD  - Division of Endocrinology, Department of Internal Medicine.
FAU - Mensenkamp, Arjen R
AU  - Mensenkamp AR
AD  - Department of Human Genetics, Radboud University Nijmegen Medical Center, 
      Nijmegen, The Netherlands.
FAU - Pfundt, Rolph
AU  - Pfundt R
AD  - Department of Human Genetics, Radboud University Nijmegen Medical Center, 
      Nijmegen, The Netherlands.
FAU - van der Luijt, Rob B
AU  - van der Luijt RB
AD  - Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - Timmers, Henri J L M
AU  - Timmers HJLM
AD  - Division of Endocrinology, Department of Internal Medicine.
FAU - Hermus, Ad R M M
AU  - Hermus ARMM
AD  - Division of Endocrinology, Department of Internal Medicine.
FAU - Kempers, Marlies J E
AU  - Kempers MJE
AD  - Department of Human Genetics, Radboud University Nijmegen Medical Center, 
      Nijmegen, The Netherlands.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
SB  - IM
MH  - Adult
MH  - Female
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Male
MH  - *Mosaicism
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Pedigree
EDAT- 2018/11/28 06:00
MHDA- 2019/02/28 06:00
CRDT- 2018/11/28 06:00
PHST- 2018/09/24 00:00 [received]
PHST- 2018/11/23 00:00 [accepted]
PHST- 2018/11/28 06:00 [pubmed]
PHST- 2019/02/28 06:00 [medline]
PHST- 2018/11/28 06:00 [entrez]
AID - EJE-18-0778 [pii]
AID - 10.1530/EJE-18-0778 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2019 Feb 1;180(2):K15-K19. doi: 10.1530/EJE-18-0778.