Characterization of PLA2G6 as a locus for dystonia-parkinsonism
Article first published online: 20 JUN 2008
Copyright © 2008 American Neurological Association
Annals of Neurology
Volume 65, Issue 1, pages 19–23, January 2009
How to Cite
Paisan-Ruiz, C., Bhatia, K. P., Li, A., Hernandez, D., Davis, M., Wood, N. W., Hardy, J., Houlden, H., Singleton, A. and Schneider, S. A. (2009), Characterization of PLA2G6 as a locus for dystonia-parkinsonism. Ann Neurol., 65: 19–23. doi: 10.1002/ana.21415
- Issue published online: 12 FEB 2009
- Article first published online: 20 JUN 2008
- Manuscript Accepted: 4 APR 2008
- Manuscript Revised: 18 MAR 2008
- Manuscript Received: 12 FEB 2008
- Intramural Research Program of the National Institute on Aging
- National Institutes of Health
- Department of Health and Human Services (Intramural Program). Grant Number: Z0I AG000958-05
- Bachmann Strauss Foundation
- Brain Research Trust, United Kingdom (JJ Astor prize studentship)
Although many recessive loci causing parkinsonism dystonia have been identified, these do not explain all cases of the disorder.
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.
We identified areas of homozygosity on chromosome 22 and, subsequently, PLA2G6 mutations.
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. Ann Neurol 2008