PMID- 30630164
OWN - NLM
STAT- MEDLINE
DCOM- 20190809
LR  - 20190809
IS  - 1423-0291 (Electronic)
IS  - 1015-2008 (Linking)
VI  - 86
IP  - 2-3
DP  - 2019
TI  - Three Novel MEN1 Variants in AIP-Negative Familial Isolated Pituitary Adenoma 
      Patients.
PG  - 128-134
LID - 10.1159/000495252 [doi]
AB  - OBJECTIVES: Pituitary adenomas (PAs) may rarely occur in well-defined hereditary 
      conditions, like multiple endocrine neoplasia type 1 (MEN1) syndrome and familial 
      isolated pituitary adenoma (FIPA) associated with germline mutations in MEN1 and 
      AIP, respectively. This study aimed to assess MEN1 genetic abnormalities in AIP 
      mutation-negative FIPA patients, not associated with MEN1 components. METHODS: 
      Among 20 patients evaluated in 13 FIPA families, 12 were previously reported as 
      AIP mutation-negative. In this study, 6 new families with 8 patients were 
      recruited. All patients were subjected to multiplex ligation-dependent probe 
      amplification to detect copy number variations in AIP and MEN1, and AIP 
      sequencing was performed in additional patients. AIP mutation-negative patients 
      were subjected to MEN1 sequencing. RESULTS: Our cohort revealed only 3 novel 
      heterozygous MEN1 variants including c.1846T>A p.(*616Argext*21), 
      rs778272737:T>C, and rs972128957:C>T in 2 families, with patients diagnosed with 
      Cushing disease, nonfunction al adenoma, and acromegaly, respectively. Among 
      them, c.1846T>A p. (*616Argext*21) is a stop codon read-through, whereas the 
      others are 3'UTR variations. MEN1 variation frequency was detected as 15%. 
      CONCLUSIONS: MEN1 alterations can be of significance in FIPA patients and 
      screening could be offered to AIP mutation-negative patients without MEN1 
      features. Further studies are needed to clarify the role of MEN1 in FIPA 
      patients.
CI  - (c) 2019 S. Karger AG, Basel.
FAU - Yarman, Sema
AU  - Yarman S
AD  - Division of Endocrinology and Metabolic Diseases, Department of Internal 
      Medicine, Faculty of Medicine, Istanbul University, Istanbul, Turkey.
FAU - Tuncer, Feyza Nur
AU  - Tuncer FN
AD  - Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul 
      University, Istanbul, Turkey, ftuncer@istanbul.edu.tr.
FAU - Serbest, Esin
AU  - Serbest E
AD  - Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul 
      University, Istanbul, Turkey.
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20190110
PL  - Switzerland
TA  - Pathobiology
JT  - Pathobiology : journal of immunopathology, molecular and cellular biology
JID - 9007504
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (aryl hydrocarbon receptor-interacting protein)
RN  - Pituitary Adenoma, Familial Isolated
MH  - Adolescent
MH  - Adult
MH  - Ambulatory Care Facilities
MH  - Cohort Studies
MH  - Female
MH  - *Genetic Variation
MH  - Growth Hormone-Secreting Pituitary Adenoma/*genetics
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*genetics
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Mutation
MH  - Pituitary Neoplasms/*genetics
MH  - Turkey
MH  - Young Adult
OTO - NOTNLM
OT  - 3'UTR variation
OT  - Familial isolated pituitary adenoma
OT  - MEN1 gene
OT  - Stop codon read-through variation
EDAT- 2019/01/11 06:00
MHDA- 2019/08/10 06:00
CRDT- 2019/01/11 06:00
PHST- 2018/07/13 00:00 [received]
PHST- 2018/11/01 00:00 [accepted]
PHST- 2019/01/11 06:00 [pubmed]
PHST- 2019/08/10 06:00 [medline]
PHST- 2019/01/11 06:00 [entrez]
AID - 000495252 [pii]
AID - 10.1159/000495252 [doi]
PST - ppublish
SO  - Pathobiology. 2019;86(2-3):128-134. doi: 10.1159/000495252. Epub 2019 Jan 10.