PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron.
Neurodegenerative disorders with high brain iron include Parkinson disease, Alzheimer disease and several childhood genetic disorders categorized as neuroaxonal dystrophies. We mapped a locus for infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA) to chromosome 22q12-q13 and identified mutations in PLA2G6, encoding a calcium-independent group VI phospholipase A2, in NBIA, INAD and the related Karak syndrome. This discovery implicates phospholipases in the pathogenesis of neurodegenerative disorders with iron dyshomeostasis.
Morgan
Neil V
NV
Section of Medical & Molecular Genetics, University of Birmingham School of Medicine, Edgbaston, Birmingham B15 2TT, UK.
Westaway
Shawn K
SK
Morton
Jenny E V
JE
Gregory
Allison
A
Gissen
Paul
P
Sonek
Scott
S
Cangul
Hakan
H
Coryell
Jason
J
Canham
Natalie
N
Nardocci
Nardo
N
Zorzi
Giovanna
G
Pasha
Shanaz
S
Rodriguez
Diana
D
Desguerre
Isabelle
I
Mubaidin
Amar
A
Bertini
Enrico
E
Trembath
Richard C
RC
Simonati
Alessandro
A
Schanen
Carolyn
C
Johnson
Colin A
CA
Levinson
Barbara
B
Woods
C Geoffrey
CG
Wilmot
Beth
B
Kramer
Patricia
P
Gitschier
Jane
J
Maher
Eamonn R
ER
Hayflick
Susan J
SJ
D001921:Brain / Q000378:metabolism*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D005260:Female; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D009154:Mutation; D019150:Neuroaxonal Dystrophies / Q000235:genetics / Q000378:metabolism; D010741:Phospholipases A / Q000737:chemistry / Q000235:genetics*; D054467:Phospholipases A2; D013577:Syndrome
D007501:Iron; D010741:Phospholipases A; D054467:Phospholipases A2