PMID- 32715270
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2472-1972 (Electronic)
IS  - 2472-1972 (Linking)
VI  - 4
IP  - 8
DP  - 2020 Aug 1
TI  - Alu-Mediated MEN1 Gene Deletion and Loss of Heterozygosity in a Patient with 
      Multiple Endocrine Neoplasia Type 1.
PG  - bvaa051
LID - 10.1210/jendso/bvaa051 [doi]
LID - bvaa051
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder 
      caused by mutations of the tumor suppressor gene MEN1. Most of the germline MEN1 
      gene mutations have been small mutations, and the whole gene deletion is rarely 
      observed. In the present study, we revealed Alu retrotransposon-mediated de novo 
      germline deletion of the whole MEN1 gene and somatic copy-neutral loss of 
      heterozygosity (LOH) in a patient with MEN1. The patient is a 39-year-old woman 
      who was referred to our department for the management of prolactinoma. She was 
      also diagnosed with primary hyperparathyroidism and suspected of MEN1. Although 
      nucleotide sequencing did not detect any MEN1 gene mutations, multiplex 
      ligation-dependent probe amplification (MLPA) revealed a large germline deletion 
      of the MEN1 gene. Subsequent quantitative polymerase chain reaction (qPCR)-based 
      copy number mapping showed a monoallelic loss of approximately 18.5-kilobase 
      region containing the whole MEN1 gene. Intriguingly, the 2 breakpoints were 
      flanked by Alu repetitive elements, suggesting the contribution of 
      Alu/Alu-mediated rearrangements (AAMR) to the whole MEN1 gene deletion. 
      Furthermore, copy number mapping using MLPA and qPCR in combination with single 
      nucleotide polymorphism analysis revealed copy-neutral LOH as a somatic event for 
      parathyroid tumorigenesis. In conclusion, copy number mapping revealed a novel 
      combination of Alu/Alu-mediated de novo germline deletion of the MEN1 gene and 
      somatic copy-neutral LOH as a cytogenetic basis for the MEN1 pathogenesis. 
      Moreover, subsequent in silico analysis highlighted the possible predisposition 
      of the MEN1 gene to Alu retrotransposon-mediated genomic deletion.
CI  - (c) Endocrine Society 2020.
FAU - Yoshiji, Satoshi
AU  - Yoshiji S
AUID- ORCID: 0000-0001-8863-2413
AD  - Department of Diabetes and Endocrinology, Tazuke Kofukai Medical Research 
      Institute, Kitano Hospital, Osaka, Japan.
FAU - Iwasaki, Yorihiro
AU  - Iwasaki Y
AUID- ORCID: 0000-0001-9787-7922
AD  - Department of Diabetes and Endocrinology, Tazuke Kofukai Medical Research 
      Institute, Kitano Hospital, Osaka, Japan.
FAU - Iwasaki, Kanako
AU  - Iwasaki K
AUID- ORCID: 0000-0003-1671-3980
AD  - Department of Diabetes and Endocrinology, Tazuke Kofukai Medical Research 
      Institute, Kitano Hospital, Osaka, Japan.
FAU - Honjo, Sachiko
AU  - Honjo S
AD  - Department of Diabetes and Endocrinology, Tazuke Kofukai Medical Research 
      Institute, Kitano Hospital, Osaka, Japan.
FAU - Hirano, Koichi
AU  - Hirano K
AD  - Department of Laboratory Medicine, Tazuke Kofukai Medical Research Institute, 
      Kitano Hospital, Osaka, Japan.
FAU - Ono, Katsuhiko
AU  - Ono K
AD  - Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, 
      Miyagi, Japan.
FAU - Yamazaki, Yuto
AU  - Yamazaki Y
AD  - Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, 
      Miyagi, Japan.
FAU - Sasano, Hironobu
AU  - Sasano H
AUID- ORCID: 0000-0002-6600-8641
AD  - Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, 
      Miyagi, Japan.
FAU - Hamasaki, Akihiro
AU  - Hamasaki A
AUID- ORCID: 0000-0002-1903-9752
AD  - Department of Diabetes and Endocrinology, Tazuke Kofukai Medical Research 
      Institute, Kitano Hospital, Osaka, Japan.
LA  - eng
PT  - Case Reports
DEP - 20200509
PL  - United States
TA  - J Endocr Soc
JT  - Journal of the Endocrine Society
JID - 101697997
PMC - PMC7371388
OTO - NOTNLM
OT  - Alu retrotransposon
OT  - Alu/Alu-mediated genomic rearrangement
OT  - loss of heterozygosity
OT  - multiple endocrine neoplasia type 1
EDAT- 2020/07/28 06:00
MHDA- 2020/07/28 06:01
PMCR- 2020/05/09
CRDT- 2020/07/28 06:00
PHST- 2020/01/21 00:00 [received]
PHST- 2020/07/28 06:00 [entrez]
PHST- 2020/07/28 06:00 [pubmed]
PHST- 2020/07/28 06:01 [medline]
PHST- 2020/05/09 00:00 [pmc-release]
AID - bvaa051 [pii]
AID - 10.1210/jendso/bvaa051 [doi]
PST - epublish
SO  - J Endocr Soc. 2020 May 9;4(8):bvaa051. doi: 10.1210/jendso/bvaa051. eCollection 
      2020 Aug 1.