Expanding the clinical phenotype of SNCA duplication carriers |
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| Authors: | Kenya Nishioka MD PhD Owen A. Ross PhD Kenji Ishii MD Jennifer M. Kachergus BS Kiichi Ishiwata PhD Mayumi Kitagawa MD PhD Satoshi Kono MD PhD Tomokazu Obi MD PhD Koichi Mizoguchi MD PhD Yuichi Inoue MD PhD Hisamasa Imai MD PhD Masashi Takanashi MD PhD Yoshikuni Mizuno MD Matthew J. Farrer PhD Nobutaka Hattori MD PhD |
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| Affiliation: | 1. Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan;2. Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA;3. Tokyo Metropolitan Institute of Gerontology, Itabashi‐ku, Tokyo, Japan;4. Department of Neurology, Sapporo Azabu Neurosurgical Hospital, Higashi‐ku, Sapporo, Japan;5. Department of Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan;6. Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan;7. Japan Somnology Center, Neuropsychiatric Research Institute, Shibuya‐ku, Tokyo, Japan;8. Department of Neurology, Tokyo Rinkai Hospital, Edogawa‐ku, Tokyo, Japan |
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| Abstract: | 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. © 2009 Movement Disorder Society |
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| Keywords: | Parkinson's disease SNCA duplication PET dementia reduced penetrance |
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