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Early‐onset familial parkinsonism due to POLG mutations
Author(s) -
Davidzon Guido,
Greene Paul,
Mancuso Michelangelo,
Klos Kevin J.,
Ahlskog J. Eric,
Hirano Michio,
DiMauro Salvatore
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20831
Subject(s) - parkinsonism , mitochondrial respiratory chain , compound heterozygosity , respiratory chain , external ophthalmoplegia , mitochondrial dna , genetics , parkin , mutation , biology , medicine , mitochondrion , gene , parkinson's disease , disease
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