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A case of α-synuclein gene duplication presenting with head-shaking movements


  • Funding agencies: This work was supported by the Strategic Research Foundation Grant-in-Aid Project for Private Universities, Grants-in-Aid for Scientific Research (80218510 [to N.H.] and 21591098 [to H.T.]), a Grant-in-Aid for Young Scientists (22790829; to M.F.), a Grant-in-Aid for Scientific Research on Innovative Areas (23129506; to M.F.) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology, and Grants-in-Aid from Research on Measures for Intractable Diseases, and Research on Health Sciences Focusing on Drug Innovation, from the Ministry of Health, Labor, and Welfare of Japan (to N.H.).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

Correspondence to: Kaori Itokawa, Department of Neurology, Saitama Medical University, 38 Moro Hongo, Moroyama-cho, Iruma-gun, Saitama 350-0495, Japan;



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.


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.


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.


The combination of SNCA gene duplication and LRRK2 G2385R variant may explain the early onset of disease in this patient. © 2012 Movement Disorder Society