title: Clinical, positron emission tomography, and pathological studies of DNAJC13 p.N855S Parkinsonism.
abstract: BACKGROUND
  Families of Dutch-German-Russian Mennonite descent with multi-incident parkinsonism have been identified as harboring a pathogenic DNAJC13 p.N855S mutation and are awaiting clinical and pathophysiological characterization.
  
  
  METHODS
  Family members were examined clinically longitudinally, and 5 underwent dopaminergic PET imaging. Four family members came to autopsy.
  
  
  RESULTS
  Of the 16 symptomatic DNAJC13 mutation carriers, 12 had clinically definite, 3 probable, and 1 possible Parkinson's disease (PD). Symptoms included bradykinesia, tremor, rigidity, and postural instability, with a mean onset of 63 years (range, 40-85) and slow progression. Eight of ten subjects who required treatment had a good levodopa response; motor complications and nonmotor symptoms were observed. Dopaminergic PET imaging revealed rostrocaudal striatal deficits typical for idiopathic PD in established disease and subtle abnormalities in incipient disease. Pathological examinations revealed Lewy body pathology.
  
  
  CONCLUSIONS
  PD associated with a DNAJC13 p.N855S mutation presents as late-onset, often slowly progressive, usually dopamine-responsive typical PD.
authors.affiliation: Pacific Parkinson's Research Center, Division of Neurology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Silke
authors.initials: S
authors.lastname: Appel-Cresswell
authors.forename: Ali H
authors.initials: AH
authors.lastname: Rajput
authors.forename: Vesna
authors.initials: V
authors.lastname: Sossi
authors.forename: Christina
authors.initials: C
authors.lastname: Thompson
authors.forename: Vanessa
authors.initials: V
authors.lastname: Silva
authors.forename: Jessamyn
authors.initials: J
authors.lastname: McKenzie
authors.forename: Katherine
authors.initials: K
authors.lastname: Dinelle
authors.forename: Siobhan E
authors.initials: SE
authors.lastname: McCormick
authors.forename: Carles
authors.initials: C
authors.lastname: Vilariño-Güell
authors.forename: A Jon
authors.initials: AJ
authors.lastname: Stoessl
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Chris A
authors.initials: CA
authors.lastname: Robinson
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: Alex
authors.initials: A
authors.lastname: Rajput
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D015259:Dopamine Agents / Q000493:pharmacokinetics; D005192:Family Health; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000175:diagnosis* / Q000235:genetics*; D049268:Positron-Emission Tomography; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000493:pharmacokinetics
chemical_list: D002247:Carbon Isotopes; C507525:DNAJC13 protein, human; D015259:Dopamine Agents; D018832:Molecular Chaperones; D019788:Fluorodeoxyglucose F18; C032811:dihydrotetrabenazine; D007980:Levodopa; D013747:Tetrabenazine
keywords: DNAJC13; Lewy Body Pathology; Mennonite; Parkinson's disease (PD); Positron Emission Tomography (PET); familial PD