Characterization of PLA2G6 as a locus for dystonia-parkinsonism.
BACKGROUND
Although many recessive loci causing parkinsonism dystonia have been identified, these do not explain all cases of the disorder.


METHODS
We used homozygosity mapping and mutational analysis in three individuals from two unrelated families who presented with adult-onset levodopa-responsive dystonia-parkinsonism, pyramidal signs and cognitive/psychiatric features, and cerebral and cerebellar atrophy on magnetic resonance imaging but absent iron in the basal ganglia.


RESULTS
We identified areas of homozygosity on chromosome 22 and, subsequently, PLA2G6 mutations.


CONCLUSIONS
PLA2G6 mutations are associated with infantile neuroaxonal dystrophy and have been reported previously to cause early cerebellar signs, and the syndrome was classified as neurodegeneration with brain iron accumulation (type 2). Our cases have neither of these previously pathognomic features. Thus, mutations in PLA2G6 should additionally be considered in patients with adult-onset dystonia-parkinsonism even with absent iron on brain imaging.
Paisan-Ruiz
Coro
C
Laboratory of Neurogenetics, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.
Bhatia
Kailash P
KP
Li
Abi
A
Hernandez
Dena
D
Davis
Mary
M
Wood
Nick W
NW
Hardy
John
J
Houlden
Henry
H
Singleton
Andrew
A
Schneider
Susanne A
SA
D000328:Adult; D002531:Cerebellum / Q000473:pathology; D002892:Chromosomes, Human, Pair 22; D004252:DNA Mutational Analysis / Q000379:methods; D004421:Dystonia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005192:Family Health; D005260:Female; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D000090463:Iron Deficiencies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D020734:Parkinsonian Disorders / Q000150:complications / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human