A novel polymerase gamma mutation in a family with ophthalmoplegia, neuropathy, and Parkinsonism.
BACKGROUND
Mutations in polymerase gamma cause progressive external ophthalmoplegia and a variety of associated symptoms and signs, including neuropathy, ataxia, hypogonadism, hearing loss, muscle weakness, and psychiatric problems. Extrapyramidal signs have been rarely described.


OBJECTIVE
To describe a family with a novel polymerase gamma mutation and autosomal dominant transmission of progressive external ophthalmoplegia, neuropathy, hypogonadism, and parkinsonism.


METHODS
Case report.


METHODS
The proband, a 49-year-old woman with incipient parkinsonism, and her 59-year-old brother with overt parkinsonian features.


METHODS
Mutation in the proband by sequencing the polymerase gamma gene and in affected relatives by restriction fragment length polymorphism analysis.


RESULTS
We found multiple mitochondrial DNA deletions in the proband's muscle and a novel missense mutation in the polymerase gamma gene (A2492G) in the proband and in her affected siblings.


CONCLUSIONS
Parkinsonism was a prominent clinical feature in this family with autosomal dominant ophthalmoplegia, multiple mitochondrial DNA deletions, and a novel mutation in the polymerase gamma gene.
Mancuso
Michelangelo
M
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Filosto
Massimiliano
M
Oh
Shin J
SJ
DiMauro
Salvatore
S
D004252:DNA Mutational Analysis; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D009886:Ophthalmoplegia / Q000235:genetics* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000473:pathology; D010375:Pedigree
D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human