PMID- 20619503
OWN - NLM
STAT- MEDLINE
DCOM- 20120615
LR  - 20220129
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Print)
IS  - 0197-4580 (Linking)
VI  - 33
IP  - 4
DP  - 2012 Apr
TI  - Widespread Lewy body and tau accumulation in childhood and adult onset 
      dystonia-parkinsonism cases with PLA2G6 mutations.
PG  - 814-23
LID - 10.1016/j.neurobiolaging.2010.05.009 [doi]
AB  - The 2 major types of neurodegeneration with brain iron accumulation (NBIA) are 
      the pantothenate kinase type 2 (PANK2)-associated neurodegeneration (PKAN) and 
      NBIA2 or infantile neuroaxonal dystrophy (INAD) due to mutations in the 
      phospholipase A2, group VI (PLA2G6) gene. We have recently demonstrated clinical 
      heterogeneity in patients with mutations in the PLA2G6 gene by identifying a 
      poorly defined subgroup of patients who present late with dystonia and 
      parkinsonism. We report the clinical and genetic features of 7 cases with PLA2G6 
      mutations. Brain was available in 5 cases with an age of death ranging from 8 to 
      36 years and showed widespread alpha-synuclein-positive Lewy pathology, which was 
      particularly severe in the neocortex, indicating that the Lewy pathology spread 
      corresponded to Braak stage 6 and was that of the "diffuse neocortical type". In 
      3 cases there was hyperphosphorylated tau accumulation in both cellular processes 
      as threads and neuronal perikarya as pretangles and neurofibrillary tangles. 
      Later onset cases tended to have less tau involvement but still severe 
      alpha-synuclein pathology. The clinical and neuropathological features clearly 
      represent a link between PLA2G6 and parkinsonian disorders.
CI  - Copyright A(c) 2012 Elsevier Inc. All rights reserved.
FAU - Paisan-Ruiz, Coro
AU  - Paisan-Ruiz C
AD  - Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
FAU - Li, Abi
AU  - Li A
FAU - Schneider, Susanne A
AU  - Schneider SA
FAU - Holton, Janice L
AU  - Holton JL
FAU - Johnson, Robert
AU  - Johnson R
FAU - Kidd, Desmond
AU  - Kidd D
FAU - Chataway, Jeremy
AU  - Chataway J
FAU - Bhatia, Kailash P
AU  - Bhatia KP
FAU - Lees, Andrew J
AU  - Lees AJ
FAU - Hardy, John
AU  - Hardy J
FAU - Revesz, Tamas
AU  - Revesz T
FAU - Houlden, Henry
AU  - Houlden H
LA  - eng
GR  - G108/638/MRC_/Medical Research Council/United Kingdom
GR  - G1001253/MRC_/Medical Research Council/United Kingdom
GR  - G0802760/MRC_/Medical Research Council/United Kingdom
GR  - G-0907/PUK_/Parkinson's UK/United Kingdom
GR  - 089698/WT_/Wellcome Trust/United Kingdom
GR  - K-0905/PUK_/Parkinson's UK/United Kingdom
GR  - MC_G1000735/MRC_/Medical Research Council/United Kingdom
GR  - G0701075/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100721
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (alpha-Synuclein)
RN  - 0 (tau Proteins)
RN  - EC 3.1.1.4 (Group VI Phospholipases A2)
RN  - EC 3.1.1.4 (PLA2G6 protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Brain/*pathology
MH  - Child
MH  - DNA Mutational Analysis
MH  - *Dystonic Disorders/genetics/metabolism/pathology
MH  - Female
MH  - Group VI Phospholipases A2/*genetics
MH  - Humans
MH  - Lewy Bodies/genetics/pathology
MH  - Male
MH  - Mutation/*genetics
MH  - *Parkinsonian Disorders/genetics/metabolism/pathology
MH  - Phenotype
MH  - alpha-Synuclein/metabolism
MH  - tau Proteins/*metabolism
PMC - PMC3657696
EDAT- 2010/07/14 06:00
MHDA- 2012/06/16 06:00
PMCR- 2012/04/01
CRDT- 2010/07/13 06:00
PHST- 2009/11/18 00:00 [received]
PHST- 2010/04/30 00:00 [revised]
PHST- 2010/05/10 00:00 [accepted]
PHST- 2010/07/13 06:00 [entrez]
PHST- 2010/07/14 06:00 [pubmed]
PHST- 2012/06/16 06:00 [medline]
PHST- 2012/04/01 00:00 [pmc-release]
AID - S0197-4580(10)00223-X [pii]
AID - 10.1016/j.neurobiolaging.2010.05.009 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2012 Apr;33(4):814-23. doi: 
      10.1016/j.neurobiolaging.2010.05.009. Epub 2010 Jul 21.