title: A case of α-synuclein gene duplication presenting with head-shaking movements.
abstract: BACKGROUND
  PARK4 is a candidate locus for familial Parkinson's disease (PD), combined with multiplication of the α-synuclein gene (SNCA). The eventual phenotype is dependent on the copy number of SNCA. Mutations in leucine-rich repeat kinase 2 (LRRK2) are also causative of parkinsonism. This report describes a man who presented at our hospital complaining of a stagger after running and difficulty in handling the mouse of a personal computer, having suffered tremors since his twenties. Nine months after treatment and discharge, he developed titubation and began to drag his right foot.
  
  
  METHODS
  We examined the patient's family pedigree for SNCA dosage, using quantitative polymerase chain reaction. We also screened this pedigree for mutations in parkin and LRRK2, using gene-sequencing techniques.
  
  
  RESULTS
  We identified the proband, his sister, and his paternal uncle as carrying a duplication of SNCA. In addition, we found that the proband and his mother carried the G2385R variant of the LRRK2, a strong risk factor for PD in Asians and the rare V1450I variant, although only the proband showed symptoms of parkinsonism. No mutations were found in parkin.
  
  
  CONCLUSIONS
  The combination of SNCA gene duplication and LRRK2 G2385R variant may explain the early onset of disease in this patient.
authors.affiliation: Department of Neurology, Saitama Medical University, Saitama, Japan. kitokawa05@yahoo.co.jp
authors.forename: Kaori
authors.initials: K
authors.lastname: Itokawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sekine
authors.forename: Manabu
authors.initials: M
authors.lastname: Funayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomiyama
authors.forename: Miki
authors.initials: M
authors.lastname: Fukui
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Tamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuda
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.forename: Nobuo
authors.initials: N
authors.lastname: Araki
mesh_terms: D000328:Adult; D002531:Cerebellum / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D005192:Family Health; D005260:Female; D020440:Gene Duplication / Q000235:genetics*; D005820:Genetic Testing; D019416:Head Movements / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009069:Movement Disorders / Q000175:diagnosis / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein