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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