This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (21)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Neurogenetics  • Movement Disorders  • Neuro-ophthalmology  • Parkinson Disease/ Parkinsonian Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

A Novel Polymerase Mutation in a Family With Ophthalmoplegia, Neuropathy, and Parkinsonism

Michelangelo Mancuso, MD; Massimiliano Filosto, MD; Shin J. Oh, MD; Salvatore DiMauro, MD

Arch Neurol. 2004;61:1777-1779.

Background  Mutations in polymerase 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 mutation and autosomal dominant transmission of progressive external ophthalmoplegia, neuropathy, hypogonadism, and parkinsonism.

Design  Case report.

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

Main Outcome Measures  Mutation in the proband by sequencing the polymerase 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 gene (A2492G) in the proband and in her affected siblings.

Conclusion  Parkinsonism was a prominent clinical feature in this family with autosomal dominant ophthalmoplegia, multiple mitochondrial DNA deletions, and a novel mutation in the polymerase gene.

Author Affiliations: Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY (Drs Mancuso, Filosto, and DiMauro), and Department of Neurology, University of Alabama at Birmingham (Dr Oh).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

The DNA polymerase {gamma} Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine
Graziewicz et al.
Hum Mol Genet 2007;16:2729-2739.
ABSTRACT | FULL TEXT  

Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease
Luoma et al.
Neurology 2007;69:1152-1159.
ABSTRACT | FULL TEXT  

Familial Parkinsonism and Ophthalmoplegia From a Mutation in the Mitochondrial DNA Helicase Twinkle
Baloh et al.
Arch Neurol 2007;64:998-1000.
ABSTRACT | FULL TEXT  

Mutation of the Linker Region of the Polymerase {gamma}-1 (POLG1) Gene Associated With Progressive External Ophthalmoplegia and Parkinsonism
Hudson et al.
Arch Neurol 2007;64:553-557.
ABSTRACT | FULL TEXT  

Parkinson syndrome, neuropathy, and myopathy caused by the mutation A8344G (MERRF) in tRNALys
Horvath et al.
Neurology 2007;68:56-58.
ABSTRACT | FULL TEXT  

POLG1 in idiopathic Parkinson disease
Tiangyou et al.
Neurology 2006;67:1698-1700.
ABSTRACT | FULL TEXT  

Mitochondrial DNA polymerase-{gamma} and human disease
Hudson and Chinnery
Hum Mol Genet 2006;15:R244-R252.
ABSTRACT | FULL TEXT  

Functional defects due to spacer-region mutations of human mitochondrial DNA polymerase in a family with an ataxia-myopathy syndrome
Luoma et al.
Hum Mol Genet 2005;14:1907-1920.
ABSTRACT | FULL TEXT