title: Neuromelanin MRI in a family with mitochondrial parkinsonism harboring a Y955C mutation in POLG1.
abstract: BACKGROUND
  Progressive external ophthalmoplegia (PEO) and parkinsonism can be caused by genetic mutations that affect mitochondrial DNA (mtDNA) maintenance. We characterized parkinsonism in a family with dominantly inherited PEO.
  
  
  METHODS
  We conducted clinical, histological and genetic analyses on two affected members suffering from PEO and parkinsonism, and reviewed the cases in the literature. To clarify parkinsonism related to multiple mtDNA deletions, we used 3-T neuromelanin magnetic resonance imaging (MRI) to assess signal changes in the substantia nigra (SN) and locus ceruleus (LC) in our patients, and compared the results to those observed in idiopathic Parkinson's disease (iPD) (n = 35).
  
  
  RESULTS
  We report the first case of a Japanese family harboring a heterozygous p.Y955C mutation in POLG1. The clinical features of parkinsonism related to the Y955C mutation in a total of 16 patients, including our two cases, are indistinguishable from iPD. However, neuromelanin MRI showed a distinct pattern in our cases compared to iPD. The neuromelanin imaging results were consistent with the neuropathological findings reported in cases of POLG1 mutations, in which neurons of the SN were profoundly affected while those in the LC were preserved.
  
  
  CONCLUSIONS
  Our results suggest that 3-T neuromelanin MRI may be useful for differentiating POLG1 mutation-associated parkinsonism from iPD, and that POLG1 mutations may cause selective neuronal loss in the SN via a mechanism different from that of iPD.
authors.affiliation: Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu, Tokyo 183-0042, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Mukai
authors.forename: Keizo
authors.initials: K
authors.lastname: Sugaya
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yabe
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Goto
authors.forename: Fusako
authors.initials: F
authors.lastname: Yokochi
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Huaying
authors.initials: H
authors.lastname: Cai
authors.forename: Hidenao
authors.initials: H
authors.lastname: Sasaki
authors.forename: Shiro
authors.initials: S
authors.lastname: Matsubara
mesh_terms: D000368:Aged; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008543:Melanins / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000473:pathology; D010375:Pedigree
chemical_list: D004272:DNA, Mitochondrial; D008543:Melanins; C014121:neuromelanin; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human
keywords: Mitochondrial DNA; Neuromelanin imaging; POLG1; Parkinsonism; Progressive external ophthalmoplegia