Expanding the clinical phenotype of SNCA duplication carriers

Kenya Nishioka, Owen A. Ross, Kenji Ishii, Jennifer M. Kachergus, Kiichi Ishiwata, Mayumi Kitagawa, Satoshi Kono, Tomokazu Obi, Koichi Mizoguchi, Yuichi Inoue, Hisamasa Imai, Masashi Takanashi, Yoshikuni Mizuno, Matthew J. Farrer, Nobutaka Hattori

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


SNCA duplication is a recognized cause of familial Parkinson's disease (PD). We aimed to explore the genetic and clinical variability in the disease manifestation. Molecular characterization was performed using real-time PCR, SNP arrays, and haplotype analysis. We further studied those patients who were found to harbor SNCA duplication with olfactory function tests, polysomnography, and PET. We identified four new families and one sporadic patient with SNCA duplication. Eleven symptomatic patients from these four families presented with parkinsonism, of which three subsequently developed dementia. The lifetime estimate of overall penetrance was 43.8%. FDG-PET study of symptomatic patients showed hypometabolism in the occipital lobe, whereas asymptomatic carriers of SNCA duplication demonstrated normal glucose metabolism. Symptomatic patients showed abnormal olfactory function and polysomnography and asymptomatic carriers showed normal results. The clinical features of SNCA duplication include parkinsonism with or without dementia. Asymptomatic carriers displayed normal test results with the eldest individual aged 79 years; thus, even a carrier of SNCA duplication may escape the development of PD. This difference in age-associated penetrance may be due to the genetic background or environmental exposures. Further studies of SNCA duplication carriers will help identify disease-modifiers and may open novel avenues for future treatment.

Original languageEnglish (US)
Pages (from-to)1811-1819
Number of pages9
JournalMovement Disorders
Issue number12
StatePublished - Sep 15 2009


  • Dementia
  • PET
  • Parkinson's disease
  • Reduced penetrance
  • SNCA duplication

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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