A novel polymerase gamma mutation in a family with ophthalmoplegia, neuropathy, and Parkinsonism

Arch Neurol. 2004 Nov;61(11):1777-9. doi: 10.1001/archneur.61.11.1777.

Abstract

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.

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 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.

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 gamma gene.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • DNA Mutational Analysis
  • DNA Polymerase gamma
  • DNA, Mitochondrial / genetics
  • DNA-Directed DNA Polymerase / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nervous System Diseases / genetics*
  • Nervous System Diseases / pathology
  • Ophthalmoplegia / genetics*
  • Ophthalmoplegia / pathology
  • Parkinsonian Disorders / genetics*
  • Parkinsonian Disorders / pathology
  • Pedigree

Substances

  • DNA, Mitochondrial
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • POLG protein, human