1. Early-onset familial parkinsonism due toPOLGmutations
- Author
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Paul Greene, Salvatore DiMauro, Michio Hirano, J. Eric Ahlskog, Michelangelo Mancuso, Kevin J. Klos, and Guido Davidzon
- Subjects
Adult ,Heterozygote ,Ophthalmoplegia, Chronic Progressive External ,Pathology ,medicine.medical_specialty ,Molecular Sequence Data ,Respiratory chain ,Genes, Recessive ,PINK1 ,DNA-Directed DNA Polymerase ,Biology ,medicine.disease_cause ,Compound heterozygosity ,DNA, Mitochondrial ,Parkin ,Tremor ,medicine ,Humans ,Amino Acid Sequence ,Age of Onset ,Muscle, Skeletal ,Genetics ,Mutation ,Multiple mitochondrial DNA deletions ,Parkinsonism ,Parkinson Disease ,DNA ,Neuromuscular Diseases ,medicine.disease ,DNA Polymerase gamma ,nervous system diseases ,Dystonia ,Peripheral neuropathy ,Neurology ,Female ,Neurology (clinical) - Abstract
Objective To define the molecular etiology of early-onset parkinsonism and peripheral neuropathy. Methods Two sisters had early-onset parkinsonism (dystonic toe curling, action tremor, masked face, bradykinesia, stooped posture, and rigidity), together with clinical and electrophysiological signs of sensorimotor axonal peripheral neuropathy. Results No mutations were found in the genes for parkin or PINK1. Muscle biopsies showed ragged-red and cytochrome c oxidase–negative fibers, and biochemistry showed decreased activities of respiratory chain complexes containing mitochondrial DNA–encoded subunits. Multiple mitochondrial DNA deletions were seen by long polymerase chain reaction, and sequencing of the POLG gene showed that the patients were compound heterozygous for two patogenic mutations. Interpretation POLG mutations can cause early-onset parkinsonism in the absence of progressive external ophthalmoplegia. Ann Neurol 2006;59:859–862
- Published
- 2006
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