PMID- 33807230
OWN - NLM
STAT- MEDLINE
DCOM- 20210811
LR  - 20210811
IS  - 2073-4425 (Electronic)
IS  - 2073-4425 (Linking)
VI  - 12
IP  - 4
DP  - 2021 Mar 31
TI  - Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T 
      (p.Leu261Phe) Variant Within a Three-Generation Family.
LID - 10.3390/genes12040512 [doi]
LID - 512
AB  - Multiple neuroendocrine neoplasia type 1 (MEN1) is a rare genetic disorder with 
      an autosomal dominant inheritance, predisposing carriers to benign and malignant 
      tumors. The phenotype of MEN1 syndrome varies between patients in terms of tumor 
      localization, age of onset, and clinical aggressiveness, even between affected 
      members within the same family. We describe a heterogenic phenotype of the MEN1 
      variant c.781C>T (LRG_509t1), which was previously reported only once in a family 
      with isolated hyperparathyroidism. A heterozygous missense variant in exon 4 of 
      the gene was identified in the sequence of the MEN1 gene, i.e., c.781C>T, leading 
      to the amino acid change p.Leu261Phe in a three-generation family. In the 
      screened family, 5/6 affected members had already developed hyperparathyroidism. 
      In the index patient and two other family members, an aggressive course of 
      pancreatic neuroendocrine tumor (insulinoma and non-functioning neuroendocrine 
      tumors) with dissemination was diagnosed. In the index patient, late diagnosis 
      and slow progression of the disseminated neuroendocrine tumor have been observed 
      (24 years of follow-up). The very rare variant of MEN1, LRG_509t1 c.781C>T 
      /p.Leu261Phe (LRG_509p1), diagnosed within a three-generation family has a 
      heterogenic clinical presentation. Further follow-up of the family members should 
      be carried out to confirm the spectrum and exact time of clinical presentation.
FAU - Gilis-Januszewska, Aleksandra
AU  - Gilis-Januszewska A
AD  - Department of Endocrinology, Jagiellonian University Medical College, 31-008 
      Cracow, Poland.
FAU - Boguslawska, Anna
AU  - Boguslawska A
AUID- ORCID: 0000-0002-1348-3924
AD  - Department of Endocrinology, Jagiellonian University Medical College, 31-008 
      Cracow, Poland.
FAU - Hasse-Lazar, Kornelia
AU  - Hasse-Lazar K
AD  - Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie 
      Institute-Oncology Centre, Gliwice Branch, 44-102 Gliwice, Poland.
FAU - Jurecka-Lubieniecka, Beata
AU  - Jurecka-Lubieniecka B
AD  - Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie 
      Institute-Oncology Centre, Gliwice Branch, 44-102 Gliwice, Poland.
FAU - Jarzab, Barbara
AU  - Jarzab B
AD  - Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie 
      Institute-Oncology Centre, Gliwice Branch, 44-102 Gliwice, Poland.
FAU - Sowa-Staszczak, Anna
AU  - Sowa-Staszczak A
AD  - Department of Endocrinology, Jagiellonian University Medical College, 31-008 
      Cracow, Poland.
FAU - Opalinska, Marta
AU  - Opalinska M
AD  - Department of Endocrinology, Jagiellonian University Medical College, 31-008 
      Cracow, Poland.
FAU - Godlewska, Magdalena
AU  - Godlewska M
AD  - Department of Endocrinology, Jagiellonian University Medical College, 31-008 
      Cracow, Poland.
FAU - Grochowska, Anna
AU  - Grochowska A
AD  - Department of Endocrinology, Jagiellonian University Medical College, 31-008 
      Cracow, Poland.
FAU - Skalniak, Anna
AU  - Skalniak A
AUID- ORCID: 0000-0001-7871-9347
AD  - Department of Endocrinology, Jagiellonian University Medical College, 31-008 
      Cracow, Poland.
FAU - Hubalewska-Dydejczyk, Alicja
AU  - Hubalewska-Dydejczyk A
AD  - Department of Endocrinology, Jagiellonian University Medical College, 31-008 
      Cracow, Poland.
LA  - eng
PT  - Journal Article
DEP - 20210331
PL  - Switzerland
TA  - Genes (Basel)
JT  - Genes
JID - 101551097
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - Amino Acid Substitution
MH  - Humans
MH  - Hyperparathyroidism/complications/*genetics
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/etiology/*genetics
MH  - *Mutation, Missense
MH  - Pedigree
MH  - Phenotype
MH  - Poland
MH  - Proto-Oncogene Proteins/*genetics
MH  - Young Adult
PMC - PMC8067145
OTO - NOTNLM
OT  - cascade genetic screening
OT  - hyperparathyroidism
OT  - multiple endocrine neoplasia type 1
OT  - pancreatic neuroendocrine tumor
OT  - pituitary tumor
COIS- The authors declare no conflict of interest.
EDAT- 2021/04/04 06:00
MHDA- 2021/08/12 06:00
PMCR- 2021/03/31
CRDT- 2021/04/03 01:26
PHST- 2021/03/05 00:00 [received]
PHST- 2021/03/25 00:00 [revised]
PHST- 2021/03/29 00:00 [accepted]
PHST- 2021/04/03 01:26 [entrez]
PHST- 2021/04/04 06:00 [pubmed]
PHST- 2021/08/12 06:00 [medline]
PHST- 2021/03/31 00:00 [pmc-release]
AID - genes12040512 [pii]
AID - genes-12-00512 [pii]
AID - 10.3390/genes12040512 [doi]
PST - epublish
SO  - Genes (Basel). 2021 Mar 31;12(4):512. doi: 10.3390/genes12040512.