Expanding the clinical phenotype of SNCA duplication carriers
Identifieur interne : 001034 ( Main/Corpus ); précédent : 001033; suivant : 001035Expanding the clinical phenotype of SNCA duplication carriers
Auteurs : 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 HattoriSource :
- Movement Disorders [ 0885-3185 ] ; 2009-09-15.
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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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DOI: 10.1002/mds.22682
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Expanding the clinical phenotype of SNCA duplication carriers</title><author><name sortKey="Nishioka, Kenya" sort="Nishioka, Kenya" uniqKey="Nishioka K" first="Kenya" last="Nishioka">Kenya Nishioka</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</mods:affiliation></affiliation></author><author><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A." last="Ross">Owen A. Ross</name><affiliation><mods:affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</mods:affiliation></affiliation></author><author><name sortKey="Ishii, Kenji" sort="Ishii, Kenji" uniqKey="Ishii K" first="Kenji" last="Ishii">Kenji Ishii</name><affiliation><mods:affiliation>Tokyo Metropolitan Institute of Gerontology, Itabashi‐ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kachergus, Jennifer M" sort="Kachergus, Jennifer M" uniqKey="Kachergus J" first="Jennifer M." last="Kachergus">Jennifer M. Kachergus</name><affiliation><mods:affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</mods:affiliation></affiliation></author><author><name sortKey="Ishiwata, Kiichi" sort="Ishiwata, Kiichi" uniqKey="Ishiwata K" first="Kiichi" last="Ishiwata">Kiichi Ishiwata</name><affiliation><mods:affiliation>Tokyo Metropolitan Institute of Gerontology, Itabashi‐ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kitagawa, Mayumi" sort="Kitagawa, Mayumi" uniqKey="Kitagawa M" first="Mayumi" last="Kitagawa">Mayumi Kitagawa</name><affiliation><mods:affiliation>Department of Neurology, Sapporo Azabu Neurosurgical Hospital, Higashi‐ku, Sapporo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kono, Satoshi" sort="Kono, Satoshi" uniqKey="Kono S" first="Satoshi" last="Kono">Satoshi Kono</name><affiliation><mods:affiliation>Department of Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan</mods:affiliation></affiliation></author><author><name sortKey="Obi, Tomokazu" sort="Obi, Tomokazu" uniqKey="Obi T" first="Tomokazu" last="Obi">Tomokazu Obi</name><affiliation><mods:affiliation>Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan</mods:affiliation></affiliation></author><author><name sortKey="Mizoguchi, Koichi" sort="Mizoguchi, Koichi" uniqKey="Mizoguchi K" first="Koichi" last="Mizoguchi">Koichi Mizoguchi</name><affiliation><mods:affiliation>Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan</mods:affiliation></affiliation></author><author><name sortKey="Inoue, Yuichi" sort="Inoue, Yuichi" uniqKey="Inoue Y" first="Yuichi" last="Inoue">Yuichi Inoue</name><affiliation><mods:affiliation>Japan Somnology Center, Neuropsychiatric Research Institute, Shibuya‐ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Imai, Hisamasa" sort="Imai, Hisamasa" uniqKey="Imai H" first="Hisamasa" last="Imai">Hisamasa Imai</name><affiliation><mods:affiliation>Department of Neurology, Tokyo Rinkai Hospital, Edogawa‐ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Takanashi, Masashi" sort="Takanashi, Masashi" uniqKey="Takanashi M" first="Masashi" last="Takanashi">Masashi Takanashi</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Mizuno, Yoshikuni" sort="Mizuno, Yoshikuni" uniqKey="Mizuno Y" first="Yoshikuni" last="Mizuno">Yoshikuni Mizuno</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J." last="Farrer">Matthew J. Farrer</name><affiliation><mods:affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</mods:affiliation></affiliation></author><author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:9CFDD6174F7B8FA0534091A488A8B9E5A9B1A40D</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1002/mds.22682</idno><idno type="url">https://api.istex.fr/document/9CFDD6174F7B8FA0534091A488A8B9E5A9B1A40D/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001034</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Expanding the clinical phenotype of SNCA duplication carriers</title><author><name sortKey="Nishioka, Kenya" sort="Nishioka, Kenya" uniqKey="Nishioka K" first="Kenya" last="Nishioka">Kenya Nishioka</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</mods:affiliation></affiliation></author><author><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A." last="Ross">Owen A. Ross</name><affiliation><mods:affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</mods:affiliation></affiliation></author><author><name sortKey="Ishii, Kenji" sort="Ishii, Kenji" uniqKey="Ishii K" first="Kenji" last="Ishii">Kenji Ishii</name><affiliation><mods:affiliation>Tokyo Metropolitan Institute of Gerontology, Itabashi‐ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kachergus, Jennifer M" sort="Kachergus, Jennifer M" uniqKey="Kachergus J" first="Jennifer M." last="Kachergus">Jennifer M. Kachergus</name><affiliation><mods:affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</mods:affiliation></affiliation></author><author><name sortKey="Ishiwata, Kiichi" sort="Ishiwata, Kiichi" uniqKey="Ishiwata K" first="Kiichi" last="Ishiwata">Kiichi Ishiwata</name><affiliation><mods:affiliation>Tokyo Metropolitan Institute of Gerontology, Itabashi‐ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kitagawa, Mayumi" sort="Kitagawa, Mayumi" uniqKey="Kitagawa M" first="Mayumi" last="Kitagawa">Mayumi Kitagawa</name><affiliation><mods:affiliation>Department of Neurology, Sapporo Azabu Neurosurgical Hospital, Higashi‐ku, Sapporo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kono, Satoshi" sort="Kono, Satoshi" uniqKey="Kono S" first="Satoshi" last="Kono">Satoshi Kono</name><affiliation><mods:affiliation>Department of Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan</mods:affiliation></affiliation></author><author><name sortKey="Obi, Tomokazu" sort="Obi, Tomokazu" uniqKey="Obi T" first="Tomokazu" last="Obi">Tomokazu Obi</name><affiliation><mods:affiliation>Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan</mods:affiliation></affiliation></author><author><name sortKey="Mizoguchi, Koichi" sort="Mizoguchi, Koichi" uniqKey="Mizoguchi K" first="Koichi" last="Mizoguchi">Koichi Mizoguchi</name><affiliation><mods:affiliation>Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan</mods:affiliation></affiliation></author><author><name sortKey="Inoue, Yuichi" sort="Inoue, Yuichi" uniqKey="Inoue Y" first="Yuichi" last="Inoue">Yuichi Inoue</name><affiliation><mods:affiliation>Japan Somnology Center, Neuropsychiatric Research Institute, Shibuya‐ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Imai, Hisamasa" sort="Imai, Hisamasa" uniqKey="Imai H" first="Hisamasa" last="Imai">Hisamasa Imai</name><affiliation><mods:affiliation>Department of Neurology, Tokyo Rinkai Hospital, Edogawa‐ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Takanashi, Masashi" sort="Takanashi, Masashi" uniqKey="Takanashi M" first="Masashi" last="Takanashi">Masashi Takanashi</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Mizuno, Yoshikuni" sort="Mizuno, Yoshikuni" uniqKey="Mizuno Y" first="Yoshikuni" last="Mizuno">Yoshikuni Mizuno</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J." last="Farrer">Matthew J. Farrer</name><affiliation><mods:affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</mods:affiliation></affiliation></author><author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2009-09-15">2009-09-15</date><biblScope unit="volume">24</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1811">1811</biblScope><biblScope unit="page" to="1819">1819</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">9CFDD6174F7B8FA0534091A488A8B9E5A9B1A40D</idno><idno type="DOI">10.1002/mds.22682</idno><idno type="ArticleID">MDS22682</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>PET</term><term>Parkinson's disease</term><term>SNCA duplication</term><term>dementia</term><term>reduced penetrance</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Kenya Nishioka MD, PhD</name><affiliations><json:string>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</json:string><json:string>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</json:string></affiliations></json:item><json:item><name>Owen A. Ross PhD</name><affiliations><json:string>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</json:string></affiliations></json:item><json:item><name>Kenji Ishii MD</name><affiliations><json:string>Tokyo Metropolitan Institute of Gerontology, Itabashi‐ku, Tokyo, Japan</json:string></affiliations></json:item><json:item><name>Jennifer M. Kachergus BS</name><affiliations><json:string>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</json:string></affiliations></json:item><json:item><name>Kiichi Ishiwata PhD</name><affiliations><json:string>Tokyo Metropolitan Institute of Gerontology, Itabashi‐ku, Tokyo, Japan</json:string></affiliations></json:item><json:item><name>Mayumi Kitagawa MD, PhD</name><affiliations><json:string>Department of Neurology, Sapporo Azabu Neurosurgical Hospital, Higashi‐ku, Sapporo, Japan</json:string></affiliations></json:item><json:item><name>Satoshi Kono MD, PhD</name><affiliations><json:string>Department of Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan</json:string></affiliations></json:item><json:item><name>Tomokazu Obi MD, PhD</name><affiliations><json:string>Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan</json:string></affiliations></json:item><json:item><name>Koichi Mizoguchi MD, PhD</name><affiliations><json:string>Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan</json:string></affiliations></json:item><json:item><name>Yuichi Inoue MD, PhD</name><affiliations><json:string>Japan Somnology Center, Neuropsychiatric Research Institute, Shibuya‐ku, Tokyo, Japan</json:string></affiliations></json:item><json:item><name>Hisamasa Imai MD, PhD</name><affiliations><json:string>Department of Neurology, Tokyo Rinkai Hospital, Edogawa‐ku, Tokyo, Japan</json:string></affiliations></json:item><json:item><name>Masashi Takanashi MD, PhD</name><affiliations><json:string>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</json:string></affiliations></json:item><json:item><name>Yoshikuni Mizuno MD</name><affiliations><json:string>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</json:string></affiliations></json:item><json:item><name>Matthew J. Farrer PhD</name><affiliations><json:string>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</json:string></affiliations></json:item><json:item><name>Nobutaka Hattori MD, PhD</name><affiliations><json:string>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SNCA duplication</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PET</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dementia</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>reduced penetrance</value></json:item></subject><articleId><json:string>MDS22682</json:string></articleId><language><json:string>eng</json:string></language><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</abstract><qualityIndicators><score>6.493</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1489</abstractCharCount><pdfWordCount>4069</pdfWordCount><pdfCharCount>27242</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>202</abstractWordCount></qualityIndicators><title>Expanding the clinical phenotype of SNCA duplication carriers</title><genre><json:string>article</json:string></genre><host><volume>24</volume><publisherId><json:string>MDS</json:string></publisherId><pages><total>9</total><last>1819</last><first>1811</first></pages><issn><json:string>0885-3185</json:string></issn><issue>12</issue><subject><json:item><value>Research Article</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8257</json:string></eissn><title>Movement Disorders</title><doi><json:string>10.1002/(ISSN)1531-8257</json:string></doi></host><publicationDate>2009</publicationDate><copyrightDate>2009</copyrightDate><doi><json:string>10.1002/mds.22682</json:string></doi><id>9CFDD6174F7B8FA0534091A488A8B9E5A9B1A40D</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/9CFDD6174F7B8FA0534091A488A8B9E5A9B1A40D/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/9CFDD6174F7B8FA0534091A488A8B9E5A9B1A40D/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/9CFDD6174F7B8FA0534091A488A8B9E5A9B1A40D/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Expanding the clinical phenotype of SNCA duplication carriers</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2009</date></publicationStmt><notesStmt><note type="content">*Potential conflict of interest: The authors declare no financial or other conflicts of interest.</note><note>MEXT of Japan - No. #20023028;</note><note>Eli‐Lilly scholarship</note><note>Juntendo University</note><note>Tokyo Medical University - No. E‐III‐2;</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Expanding the clinical phenotype of SNCA duplication carriers</title><author><persName><forename type="first">Kenya</forename><surname>Nishioka</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</affiliation><affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</affiliation></author><author><persName><forename type="first">Owen A.</forename><surname>Ross</surname></persName><roleName type="degree">PhD</roleName><affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</affiliation></author><author><persName><forename type="first">Kenji</forename><surname>Ishii</surname></persName><roleName type="degree">MD</roleName><affiliation>Tokyo Metropolitan Institute of Gerontology, Itabashi‐ku, Tokyo, Japan</affiliation></author><author><persName><forename type="first">Jennifer M.</forename><surname>Kachergus</surname></persName><roleName type="degree">BS</roleName><affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</affiliation></author><author><persName><forename type="first">Kiichi</forename><surname>Ishiwata</surname></persName><roleName type="degree">PhD</roleName><affiliation>Tokyo Metropolitan Institute of Gerontology, Itabashi‐ku, Tokyo, Japan</affiliation></author><author><persName><forename type="first">Mayumi</forename><surname>Kitagawa</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Sapporo Azabu Neurosurgical Hospital, Higashi‐ku, Sapporo, Japan</affiliation></author><author><persName><forename type="first">Satoshi</forename><surname>Kono</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan</affiliation></author><author><persName><forename type="first">Tomokazu</forename><surname>Obi</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan</affiliation></author><author><persName><forename type="first">Koichi</forename><surname>Mizoguchi</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan</affiliation></author><author><persName><forename type="first">Yuichi</forename><surname>Inoue</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Japan Somnology Center, Neuropsychiatric Research Institute, Shibuya‐ku, Tokyo, Japan</affiliation></author><author><persName><forename type="first">Hisamasa</forename><surname>Imai</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Tokyo Rinkai Hospital, Edogawa‐ku, Tokyo, Japan</affiliation></author><author><persName><forename type="first">Masashi</forename><surname>Takanashi</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</affiliation></author><author><persName><forename type="first">Yoshikuni</forename><surname>Mizuno</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</affiliation></author><author><persName><forename type="first">Matthew J.</forename><surname>Farrer</surname></persName><roleName type="degree">PhD</roleName><affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</affiliation></author><author><persName><forename type="first">Nobutaka</forename><surname>Hattori</surname></persName><roleName type="degree">MD, PhD</roleName><note type="correspondence"><p>Correspondence: Department of Neurology, Juntendo University School of Medicine, 2‐1‐1 Hongo, Bunkyo‐ku, Tokyo 113‐8421, Japan</p></note><affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2009-09-15"></date><biblScope unit="volume">24</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1811">1811</biblScope><biblScope unit="page" to="1819">1819</biblScope></imprint></monogr><idno type="istex">9CFDD6174F7B8FA0534091A488A8B9E5A9B1A40D</idno><idno type="DOI">10.1002/mds.22682</idno><idno type="ArticleID">MDS22682</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>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</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson's disease</term></item><item><term>SNCA duplication</term></item><item><term>PET</term></item><item><term>dementia</term></item><item><term>reduced penetrance</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2009-01-28">Received</change><change when="2009-05-27">Registration</change><change when="2009-09-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/9CFDD6174F7B8FA0534091A488A8B9E5A9B1A40D/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov. Disord.</title></titleGroup></publicationMeta><publicationMeta level="part" position="120"><doi origin="wiley" registered="yes">10.1002/mds.v24:12</doi><numberingGroup><numbering type="journalVolume" number="24">24</numbering><numbering type="journalIssue">12</numbering></numberingGroup><coverDate startDate="2009-09-15">15 September 2009</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="13" status="forIssue"><doi origin="wiley" registered="yes">10.1002/mds.22682</doi><idGroup><id type="unit" value="MDS22682"></id></idGroup><countGroup><count type="pageTotal" number="9"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 2009 Movement Disorder Society</copyright><eventGroup><event type="manuscriptReceived" date="2009-01-28"></event><event type="manuscriptRevised" date="2009-03-25"></event><event type="manuscriptAccepted" date="2009-05-27"></event><event type="publishedOnlineEarlyUnpaginated" date="2009-06-26"></event><event type="firstOnline" date="2009-06-26"></event><event type="publishedOnlineFinalForm" date="2009-09-11"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.15 mode:FullText source:FullText result:FullText" date="2010-07-15"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-02"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-31"></event></eventGroup><numberingGroup><numbering type="pageFirst">1811</numbering><numbering type="pageLast">1819</numbering></numberingGroup><correspondenceTo>Department of Neurology, Juntendo University School of Medicine, 2‐1‐1 Hongo, Bunkyo‐ku, Tokyo 113‐8421, Japan</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS22682.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="2"></count><count type="referenceTotal" number="34"></count><count type="wordTotal" number="5495"></count></countGroup><titleGroup><title type="main" xml:lang="en">Expanding the clinical phenotype of <i>SNCA</i> duplication carriers<link href="#fn1"></link></title><title type="short" xml:lang="en">Clinical Phenotype of SNCA Duplication Carriers</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Kenya</givenNames><familyName>Nishioka</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Owen A.</givenNames><familyName>Ross</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Kenji</givenNames><familyName>Ishii</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Jennifer M.</givenNames><familyName>Kachergus</familyName><degrees>BS</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Kiichi</givenNames><familyName>Ishiwata</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Mayumi</givenNames><familyName>Kitagawa</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Satoshi</givenNames><familyName>Kono</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Tomokazu</givenNames><familyName>Obi</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Koichi</givenNames><familyName>Mizoguchi</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af7"><personName><givenNames>Yuichi</givenNames><familyName>Inoue</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af8"><personName><givenNames>Hisamasa</givenNames><familyName>Imai</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Masashi</givenNames><familyName>Takanashi</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Yoshikuni</givenNames><familyName>Mizuno</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au14" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Matthew J.</givenNames><familyName>Farrer</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au15" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Nobutaka</givenNames><familyName>Hattori</familyName><degrees>MD, PhD</degrees></personName><contactDetails><email>nhattori@juntendo.ac.jp</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="JP" type="organization"><unparsedAffiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="JP" type="organization"><unparsedAffiliation>Tokyo Metropolitan Institute of Gerontology, Itabashi‐ku, Tokyo, Japan</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="JP" type="organization"><unparsedAffiliation>Department of Neurology, Sapporo Azabu Neurosurgical Hospital, Higashi‐ku, Sapporo, Japan</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="JP" type="organization"><unparsedAffiliation>Department of Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="JP" type="organization"><unparsedAffiliation>Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="JP" type="organization"><unparsedAffiliation>Japan Somnology Center, Neuropsychiatric Research Institute, Shibuya‐ku, Tokyo, Japan</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="JP" type="organization"><unparsedAffiliation>Department of Neurology, Tokyo Rinkai Hospital, Edogawa‐ku, Tokyo, Japan</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson's disease</keyword><keyword xml:id="kwd2"><i>SNCA</i> duplication</keyword><keyword xml:id="kwd3">PET</keyword><keyword xml:id="kwd4">dementia</keyword><keyword xml:id="kwd5">reduced penetrance</keyword></keywordGroup><fundingInfo><fundingAgency>MEXT of Japan</fundingAgency><fundingNumber>#20023028</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Eli‐Lilly scholarship</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Juntendo University</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Tokyo Medical University</fundingAgency><fundingNumber>E‐III‐2</fundingNumber></fundingInfo><supportingInformation><p> Additional Supporting Information may be found in the online version of this article. </p><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds22682:MDS_22682_sm_suppinfo"></mediaResource><caption>Supplementary Data</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds22682:MDS_22682_sm_suppfig1"></mediaResource><caption>Supplementary Figure 1</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds22682:MDS_22682_sm_suppfig2"></mediaResource><caption>Supplementary Figure 2</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds22682:SupFigLeg"></mediaResource><caption>Legends to Supplementary Figures</caption></supportingInfoItem></supportingInformation><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p><i>SNCA</i> 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 <i>SNCA</i> duplication with olfactory function tests, polysomnography, and PET. We identified four new families and one sporadic patient with <i>SNCA</i> 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 <i>SNCA</i> duplication demonstrated normal glucose metabolism. Symptomatic patients showed abnormal olfactory function and polysomnography and asymptomatic carriers showed normal results. The clinical features of <i>SNCA</i> 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 <i>SNCA</i> 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 <i>SNCA</i> duplication carriers will help identify disease‐modifiers and may open novel avenues for future treatment. © 2009 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Potential conflict of interest: The authors declare no financial or other conflicts of interest.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Expanding the clinical phenotype of SNCA duplication carriers</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Clinical Phenotype of SNCA Duplication Carriers</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Expanding the clinical phenotype of</title></titleInfo><name type="personal"><namePart type="given">Kenya</namePart><namePart type="family">Nishioka</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</affiliation><affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Owen A.</namePart><namePart type="family">Ross</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kenji</namePart><namePart type="family">Ishii</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Tokyo Metropolitan Institute of Gerontology, Itabashi‐ku, Tokyo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jennifer M.</namePart><namePart type="family">Kachergus</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kiichi</namePart><namePart type="family">Ishiwata</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Tokyo Metropolitan Institute of Gerontology, Itabashi‐ku, Tokyo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mayumi</namePart><namePart type="family">Kitagawa</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Sapporo Azabu Neurosurgical Hospital, Higashi‐ku, Sapporo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Satoshi</namePart><namePart type="family">Kono</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Tomokazu</namePart><namePart type="family">Obi</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Koichi</namePart><namePart type="family">Mizoguchi</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yuichi</namePart><namePart type="family">Inoue</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Japan Somnology Center, Neuropsychiatric Research Institute, Shibuya‐ku, Tokyo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hisamasa</namePart><namePart type="family">Imai</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Tokyo Rinkai Hospital, Edogawa‐ku, Tokyo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Masashi</namePart><namePart type="family">Takanashi</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yoshikuni</namePart><namePart type="family">Mizuno</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Matthew J.</namePart><namePart type="family">Farrer</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nobutaka</namePart><namePart type="family">Hattori</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Juntendo University School of Medicine, Bunkyo‐ku, Tokyo, Japan</affiliation><description>Correspondence: Department of Neurology, Juntendo University School of Medicine, 2‐1‐1 Hongo, Bunkyo‐ku, Tokyo 113‐8421, Japan</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2009-09-15</dateIssued><dateCaptured encoding="w3cdtf">2009-01-28</dateCaptured><dateValid encoding="w3cdtf">2009-05-27</dateValid><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">3</extent><extent unit="tables">2</extent><extent unit="references">34</extent><extent unit="words">5495</extent></physicalDescription><abstract lang="en">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</abstract><note type="content">*Potential conflict of interest: The authors declare no financial or other conflicts of interest.</note><note type="funding">MEXT of Japan - No. #20023028; </note><note type="funding">Eli‐Lilly scholarship</note><note type="funding">Juntendo University</note><note type="funding">Tokyo Medical University - No. E‐III‐2; </note><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>SNCA duplication</topic><topic>PET</topic><topic>dementia</topic><topic>reduced penetrance</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><genre type="Journal">journal</genre><note type="content"> Additional Supporting Information may be found in the online version of this article.Supporting Info Item: Supplementary Data - Supplementary Figure 1 - Supplementary Figure 2 - Legends to Supplementary Figures - </note><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>24</number></detail><detail type="issue"><caption>no.</caption><number>12</number></detail><extent unit="pages"><start>1811</start><end>1819</end><total>9</total></extent></part></relatedItem><identifier type="istex">9CFDD6174F7B8FA0534091A488A8B9E5A9B1A40D</identifier><identifier type="DOI">10.1002/mds.22682</identifier><identifier type="ArticleID">MDS22682</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2009 Movement Disorder Society</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Expanding the clinical phenotype of SNCA duplication carriers
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| This area was generated with Dilib version V0.6.23. |  |