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

Abstract

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. To describe a family with a novel polymerase gamma mutation and autosomal dominant transmission of progressive external ophthalmoplegia, neuropathy, hypogonadism, and parkinsonism. Case report. The proband, a 49-year-old woman with incipient parkinsonism, and her 59-year-old brother with overt parkinsonian features. Mutation in the proband by sequencing the polymerase gamma gene and in affected relatives by restriction fragment length polymorphism analysis. 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. 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.