PMID- 32055598
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220412
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 8
IP  - 1
DP  - 2020 Jan
TI  - A proposed synergistic effect of CSF1R and NMUR2 variants contributes to binge 
      eating in hereditary diffuse leukoencephalopathy with spheroids.
PG  - 7
LID - 10.21037/atm.2019.11.30 [doi]
LID - 7
AB  - BACKGROUND: The genetic mechanisms of binge eating (BE) as a disease identity 
      remain obscure. BE is usually viewed as a part of the behavioral variant of 
      frontotemporal dementia (bvFTD) features. We encountered a family with hereditary 
      diffuse leukoencephalopathy with spheroids (HDLS) that manifested uniformly with 
      binge-eating-onset dementia. The genetic factors associated with the rare 
      phenotype were investigated. METHODS: The detailed phenotypes of the patients 
      were described. We performed whole-exome sequencing (WES) of family members and 
      repeat-primed PCR to analyze the patients' expansion size of C9orf72, a 
      well-established gene causing FTD. The WES results of additional HDLS patients 
      without BE manifestations were also investigated. RESULTS: All affected 
      individuals had a BE-dementia-epilepsy pattern of disease progression. A 
      recurrent disease-causing mutation in CSF1R established the diagnosis of HDLS in 
      the family. No abnormalities in the expansion size of C9orf72 were detected. The 
      concurrence of a recurrent CSF1R mutation and a rare variant in NMUR2, a gene 
      functionally related to BE, was revealed in the affected family members. No 
      potentially pathogenic variants in other known BE-associated genes were 
      identified. Both the NMUR2 variant and the CSF1R mutation cosegregated with the 
      BE-dementia-epilepsy phenotype in the family. In three additional HDLS patients 
      without BE, no pathogenic variants in NMUR2 were detected. CONCLUSIONS: We 
      propose that synergistic genetic effects of NMUR2 and CSF1R variants may exist 
      and contribute to the development of the BE phenotype in HDLS. NMUR2 is one of 
      the potential susceptible genes in BE and may contribute in a background of a 
      disrupted structural neuronetwork. Further studies in other BE-related disorders 
      are required.
CI  - 2020 Annals of Translational Medicine. All rights reserved.
FAU - Liu, Qing
AU  - Liu Q
AD  - Department of Neurology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences & Peking Union Medical College (CAMS & PUMCH), Beijing 
      100730, China.
FAU - Guo, Xia-Nan
AU  - Guo XN
AD  - Department of Neurology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences & Peking Union Medical College (CAMS & PUMCH), Beijing 
      100730, China.
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, CAMS & PUMCH, Beijing 100005, China.
AD  - Department of Nephrology, the First Affiliated Hospital of Dalian Medical 
      University, Dalian Medical University, Dalian 116011, China.
FAU - Liu, Cai-Yan
AU  - Liu CY
AD  - Department of Neurology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences & Peking Union Medical College (CAMS & PUMCH), Beijing 
      100730, China.
FAU - Xu, Wei-Hai
AU  - Xu WH
AD  - Department of Neurology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences & Peking Union Medical College (CAMS & PUMCH), Beijing 
      100730, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC6995742
OTO - NOTNLM
OT  - Binge eating (BE)
OT  - NMUR2
OT  - genetic modifier
OT  - hereditary diffuse leukoencephalopathy with spheroids (HDLS)
COIS- Conflicts of Interest: The authors have no conflicts of interest to declare.
EDAT- 2020/02/15 06:00
MHDA- 2020/02/15 06:01
PMCR- 2020/01/01
CRDT- 2020/02/15 06:00
PHST- 2020/02/15 06:00 [entrez]
PHST- 2020/02/15 06:00 [pubmed]
PHST- 2020/02/15 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - atm-08-01-7 [pii]
AID - 10.21037/atm.2019.11.30 [doi]
PST - ppublish
SO  - Ann Transl Med. 2020 Jan;8(1):7. doi: 10.21037/atm.2019.11.30.