PMID- 32299109
OWN - NLM
STAT- MEDLINE
DCOM- 20210817
LR  - 20210817
IS  - 1439-4286 (Electronic)
IS  - 0018-5043 (Linking)
VI  - 52
IP  - 11
DP  - 2020 Nov
TI  - Identification of Novel Variants in MEN1: A Study Conducted with Four Multiple 
      Endocrine Neoplasia Type 1 Patients.
PG  - 788-795
LID - 10.1055/a-1147-1375 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited 
      endocrine tumor syndrome caused by inactivating variants of the MEN1 gene. The 
      aim of this study is to explore the clinical and genetic characteristics of four 
      MEN1 patients. We isolated genomic deoxyribonucleic acid from lymphocytes, 
      parathyroid, and thymic tumoral tissue specimens from the MEN1 patients. All 
      exons of the MEN1 and CDNK1B genes and adjacent exon-intron sequences were 
      amplified by polymerase chain reaction and subsequently sequenced. Further, the 
      splice alterations were studied by sequencing the amplified RT-PCR products for 
      MEN1 cDNA. We identified four heterozygous MEN1 germline variants: c.564delC, 
      c.1268G>A, IVS5+5delG, and c.1546_1547insC. Both c.564delC and IVS5+5delG were 
      novel variants. The impact of the MEN1 splice variant, IVS5+5delG, was evaluated 
      using bioinformatics and in vitro analyses. The analyses indicated that this 
      variant resulted in skipping of the neighboring exon and was disease-causing. Two 
      novel somatic variants, c.249_252delGTCT and c.313_314insC, were found. 
      Additionally, loss of heterozygosity (LOH) for the MEN1 locus (IVS5+5delG and 
      c.564delC) was found in tumor tissue samples from the MEN1 patients, consistent 
      with Knudson's two-hit mechanism. We identified four MEN1 germline variants and 
      two novel somatic variants. Early recognition of the phenotype coupled with 
      variant screening of the MEN1 gene is the key to diagnosing and treating MEN1 
      effectively at an early stage.
CI  - Thieme. All rights reserved.
FAU - Hu, Wen-Mu
AU  - Hu WM
AD  - Department of Endocrinology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
FAU - Zhang, Qin
AU  - Zhang Q
AD  - Department of Endocrinology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
FAU - Huang, Li-Hua
AU  - Huang LH
AD  - Department of Endocrinology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
FAU - Mo, Zhao-Hui
AU  - Mo ZH
AD  - Department of Endocrinology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
FAU - Long, Xiao-Dan
AU  - Long XD
AD  - Department of Endocrinology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
FAU - Yang, You-Bo
AU  - Yang YB
AD  - Department of Endocrinology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
FAU - Yang, Wen-Jun
AU  - Yang WJ
AD  - Department of Endocrinology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
FAU - Liu, Jun
AU  - Liu J
AD  - Department of Endocrinology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
FAU - Jin, Ping
AU  - Jin P
AD  - Department of Endocrinology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
LA  - eng
GR  - National Natural Science Foundation of China/81670730/
GR  - National Natural Science Foundation of China/81100583/
PT  - Case Reports
PT  - Journal Article
DEP - 20200416
PL  - Germany
TA  - Horm Metab Res
JT  - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et 
      metabolisme
JID - 0177722
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/genetics/*pathology
MH  - *Mutation
MH  - *Phenotype
MH  - Proto-Oncogene Proteins/*genetics
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/04/17 06:00
MHDA- 2021/08/18 06:00
CRDT- 2020/04/17 06:00
PHST- 2020/04/17 06:00 [pubmed]
PHST- 2021/08/18 06:00 [medline]
PHST- 2020/04/17 06:00 [entrez]
AID - 10.1055/a-1147-1375 [doi]
PST - ppublish
SO  - Horm Metab Res. 2020 Nov;52(11):788-795. doi: 10.1055/a-1147-1375. Epub 2020 Apr 
      16.