Familial parkinsonism and ophthalmoplegia from a mutation in the mitochondrial DNA helicase twinkle

Arch Neurol. 2007 Jul;64(7):998-1000. doi: 10.1001/archneur.64.7.998.


Objective: To describe the clinical phenotype and genetic basis of a family with autosomal dominant progressive external ophthalmoplegia and parkinsonism from a Twinkle mutation.

Design: All coding exons of POLG1, Twinkle (aka C10ORF2, PEO1), and ANT1 (SLC25A4) were sequenced in the proband with targeted sequencing of the Twinkle gene in all additional subjects.

Subjects: Members of a 3-generation family followed up in a neuromuscular disease center for dominantly inherited progressive external ophthalmoplegia.

Results: We identified a heterozygous G1121A mutation (R374Q) in exon 1 of Twinkle that segregated with the disease phenotype in all affected family members. No pathogenic mutations were present in POLG1 or ANT1.

Conclusion: This finding broadens the clinical spectrum of Twinkle gene mutations and further implicates loss of mitochondrial DNA integrity in the pathogenesis of Parkinson disease.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Helicases / genetics*
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genotype
  • Humans
  • Middle Aged
  • Mitochondrial Diseases / enzymology
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / physiopathology
  • Mitochondrial Proteins
  • Mutation / genetics*
  • Ophthalmoplegia, Chronic Progressive External / enzymology
  • Ophthalmoplegia, Chronic Progressive External / genetics*
  • Ophthalmoplegia, Chronic Progressive External / physiopathology
  • Parkinsonian Disorders / enzymology
  • Parkinsonian Disorders / genetics*
  • Parkinsonian Disorders / physiopathology
  • Pedigree
  • Penetrance
  • Phenotype


  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • DNA Helicases
  • TWNK protein, human