A novel polymerase γ mutation in a family with ophthalmoplegia, neuropathy, and parkinsonism

Background: Mutations in polymerase γ 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 γ 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 γ 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 γ 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 γ gene.