PMID- 35735085
OWN - NLM
STAT- MEDLINE
DCOM- 20220624
LR  - 20220716
IS  - 2320-2890 (Electronic)
IS  - 2319-4170 (Print)
IS  - 2319-4170 (Linking)
VI  - 44
IP  - 6 Suppl 1
DP  - 2021 Dec
TI  - A CD33 frameshift variant is associated with neuromyelitis optica spectrum 
      disorders.
PG  - S93-S100
LID - S2319-4170(20)30125-6 [pii]
LID - 10.1016/j.bj.2020.07.007 [doi]
AB  - BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare 
      neuroimmunology disorder predominantly affecting the East Asia population, the 
      reason for this preference remains unknown. Genetic factors such as polymorphisms 
      in human leukocyte antigen (HLA) and interleukins (IL) genes have been reported. 
      Although the familial occurrence of NMOSD is rare, it supports that genetic 
      factors may play a role. METHODS: Whole exome sequencing (WES) study was 
      performed on the affected mother and daughter, as well as the unaffected father 
      in a Taiwanese family with NMOSD. A cohort of 19 sporadic patients with aquaporin 
      4 antibody (AQP4-Ab) positive NMOSD was also recruited; all fulfilled the 2015 
      International NMOSD Diagnosis Criteria. Sanger sequencing was performed on exon 4 
      of the CD33 gene on the sporadic NMOSD cohort. RESULTS: WES study revealed a 19 
      base pair deletion in exon 4 of the CD33 gene, resulting in frameshift premature 
      truncating protein, which segregated with the affected status. CD33 was the most 
      likely candidate gene due to its known function in immune regulation. A total of 
      19 sporadic NMOSD patients were tested using Sanger sequencing, including 3 
      patients with other concomitant autoimmune disorders. Two additional NMOSD 
      patients were found to have the same CD33 frameshift variant, which accounts for 
      19.04% of all NMOSD patients, and 15% following correction for the familial 
      cases; compared to 2% in Taiwanese population controls. CONCLUSION: In this 
      study, we identified a 19 base pair deletion in the CD33 gene may be a potential 
      risk locus for NMOSD, which is predicted to cause loss of function of CD33. The 
      loss of CD33 inhibitory function may affect the regulation of the immune system 
      in NMOSD patients. This finding requires further larger cohorts of NMOSD patients 
      and functional study to corroborate.
CI  - Copyright (c) 2020 Chang Gung University. Published by Elsevier B.V. All rights 
      reserved.
FAU - Huang, Yu-Ju
AU  - Huang YJ
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 
      Taiwan.
FAU - Lee, Jun-Jun
AU  - Lee JJ
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 
      Taiwan; Department of Information Management, National Sun Yat-sen University, 
      Kaohsiung, Taiwan.
FAU - Fan, Wen-Lan
AU  - Fan WL
AD  - Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital at Linkou, Taiwan.
FAU - Hsu, Che-Wei
AU  - Hsu CW
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 
      Taiwan.
FAU - Tsai, Nai-Wen
AU  - Tsai NW
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 
      Taiwan.
FAU - Lu, Cheng-Hsien
AU  - Lu CH
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 
      Taiwan.
FAU - Chang, Wen-Neng
AU  - Chang WN
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 
      Taiwan.
FAU - Tsai, Meng-Han
AU  - Tsai MH
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 
      Taiwan; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, 
      Taiwan. Electronic address: menghan@cgmh.org.tw.
LA  - eng
PT  - Journal Article
DEP - 20200727
PL  - United States
TA  - Biomed J
JT  - Biomedical journal
JID - 101599820
RN  - 0 (Aquaporin 4)
RN  - 0 (Autoantibodies)
RN  - 0 (CD33 protein, human)
RN  - 0 (Sialic Acid Binding Ig-like Lectin 3)
RN  - 0 (anti-aquaporin 4 autoantibody)
SB  - IM
MH  - Aquaporin 4
MH  - Autoantibodies
MH  - Cohort Studies
MH  - Humans
MH  - *Neuromyelitis Optica/epidemiology/genetics
MH  - Sialic Acid Binding Ig-like Lectin 3
PMC - PMC9038945
OTO - NOTNLM
OT  - AQP4
OT  - CD33
OT  - Neuromyelitis optica
OT  - Siglec-3
COIS- Conflicts of interest All authors reported no conflicts of interest associated 
      with this publication and there has no financial support for this work that could 
      influence the study outcome.
EDAT- 2022/06/24 06:00
MHDA- 2022/06/25 06:00
PMCR- 2020/07/27
CRDT- 2022/06/23 05:23
PHST- 2020/01/01 00:00 [received]
PHST- 2020/06/09 00:00 [revised]
PHST- 2020/07/22 00:00 [accepted]
PHST- 2022/06/23 05:23 [entrez]
PHST- 2022/06/24 06:00 [pubmed]
PHST- 2022/06/25 06:00 [medline]
PHST- 2020/07/27 00:00 [pmc-release]
AID - S2319-4170(20)30125-6 [pii]
AID - 10.1016/j.bj.2020.07.007 [doi]
PST - ppublish
SO  - Biomed J. 2021 Dec;44(6 Suppl 1):S93-S100. doi: 10.1016/j.bj.2020.07.007. Epub 
      2020 Jul 27.