PMID- 37285793
OWN - NLM
STAT- MEDLINE
DCOM- 20230703
LR  - 20231116
IS  - 1873-5126 (Electronic)
IS  - 1353-8020 (Linking)
VI  - 112
DP  - 2023 Jul
TI  - A systematic analysis of genotype-phenotype associations with PLA2G6.
PG  - 105477
LID - S1353-8020(23)00200-6 [pii]
LID - 10.1016/j.parkreldis.2023.105477 [doi]
AB  - BACKGROUND: PLA2G6-associated neurodegeneration (PLAN) can be categorized into 
      infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (aNAD), 
      neurodegeneration with brain iron accumulation (NBIA), and early-onset 
      parkinsonism (EOP). OBJECTIVES: To determine the genotype-phenotype association 
      in PLAN. METHODS: "PLA2G6" or "PARK14" or "phospholipase A2 group VI" or "iPLA2beta" 
      were searched across MEDLINE from June 23, 1997, to March 1, 2023. A total of 391 
      patients were identified, and 340 patients of them were finally included in the 
      assessment. RESULTS: The loss of function (LOF) mutation ratios were 
      significantly different (p < 0.001), highest in INAD, followed by NBIA, aNAD, and 
      EOP. Four ensemble scores (i.e., BayesDel, VARITY, ClinPred, and MetaRNN) were 
      assessed to predict the deleteriousness of missense mutations and demonstrated 
      significant differences (p < 0.001). Binary logistic regression analyses 
      demonstrated that LOF mutations were independently associated with brain iron 
      accumulation (p = 0.006) and ataxia (p = 0.025). CONCLUSIONS: LOF or more 
      deleterious missense mutations are more likely to promote the development of 
      serious phenotype of PLAN, and LOF mutations are independently associated with 
      brain iron accumulation and ataxia.
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Xue, Jian
AU  - Xue J
AD  - Department of Neurology and Suzhou Clinical Research Center of Neurological 
      Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
FAU - Ding, Dong-Xue
AU  - Ding DX
AD  - Department of Neurology, The First Affiliated Hospital of Soochow University, 
      Suzhou, China.
FAU - Xu, Guang-Yu
AU  - Xu GY
AD  - Soochow University, Suzhou, China.
FAU - Wang, Pu-Zhi
AU  - Wang PZ
AD  - Department of Neurology and Suzhou Clinical Research Center of Neurological 
      Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
FAU - Ge, Yi-Lun
AU  - Ge YL
AD  - Department of Neurology and Suzhou Clinical Research Center of Neurological 
      Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
FAU - Zhang, Jin-Ru
AU  - Zhang JR
AD  - Department of Neurology and Suzhou Clinical Research Center of Neurological 
      Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
FAU - Cheng, Xiao-Yu
AU  - Cheng XY
AD  - Department of Neurology and Suzhou Clinical Research Center of Neurological 
      Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
FAU - Wang, Yi-Ming
AU  - Wang YM
AD  - Department of Neurology and Suzhou Clinical Research Center of Neurological 
      Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
FAU - Jin, Hong
AU  - Jin H
AD  - Department of Neurology and Suzhou Clinical Research Center of Neurological 
      Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
FAU - Luo, Si-Yang
AU  - Luo SY
AD  - Soochow University, Suzhou, China.
FAU - Zheng, Yu-Han
AU  - Zheng YH
AD  - Soochow University, Suzhou, China.
FAU - Chen, Jing
AU  - Chen J
AD  - Department of Neurology and Suzhou Clinical Research Center of Neurological 
      Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
FAU - Wang, Fen
AU  - Wang F
AD  - Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of 
      Neuroscience, Soochow University, Suzhou, China.
FAU - Li, Dan
AU  - Li D
AD  - Department of Neurology, Suqian First People's Hospital, Suqian, China.
FAU - Mao, Cheng-Jie
AU  - Mao CJ
AD  - Department of Neurology and Suzhou Clinical Research Center of Neurological 
      Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China; 
      Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of 
      Neuroscience, Soochow University, Suzhou, China.
FAU - Li, Kai
AU  - Li K
AD  - Department of Neurology and Suzhou Clinical Research Center of Neurological 
      Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China. 
      Electronic address: liskai@126.com.
FAU - Liu, Chun-Feng
AU  - Liu CF
AD  - Department of Neurology and Suzhou Clinical Research Center of Neurological 
      Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China; 
      Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of 
      Neuroscience, Soochow University, Suzhou, China; Department of Neurology, Suqian 
      First People's Hospital, Suqian, China. Electronic address: 
      liuchunfeng@suda.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230601
PL  - England
TA  - Parkinsonism Relat Disord
JT  - Parkinsonism & related disorders
JID - 9513583
RN  - E1UOL152H7 (Iron)
RN  - EC 3.1.1.4 (Group VI Phospholipases A2)
RN  - NBIA2B
SB  - IM
MH  - Humans
MH  - Mutation/genetics
MH  - *Parkinsonian Disorders/genetics
MH  - Genetic Association Studies
MH  - *Neuroaxonal Dystrophies/genetics
MH  - Iron
MH  - Ataxia
MH  - Group VI Phospholipases A2/genetics
OTO - NOTNLM
OT  - Genotype
OT  - PLA2G6
OT  - Phenotype
COIS- Declaration of competing interest None of the authors has any conflict of 
      interest to disclose.
EDAT- 2023/06/08 01:08
MHDA- 2023/07/03 06:41
CRDT- 2023/06/07 18:09
PHST- 2023/01/03 00:00 [received]
PHST- 2023/05/23 00:00 [revised]
PHST- 2023/05/30 00:00 [accepted]
PHST- 2023/07/03 06:41 [medline]
PHST- 2023/06/08 01:08 [pubmed]
PHST- 2023/06/07 18:09 [entrez]
AID - S1353-8020(23)00200-6 [pii]
AID - 10.1016/j.parkreldis.2023.105477 [doi]
PST - ppublish
SO  - Parkinsonism Relat Disord. 2023 Jul;112:105477. doi: 
      10.1016/j.parkreldis.2023.105477. Epub 2023 Jun 1.