Clinical and genetic features of cervical dystonia in a large multicenter cohort
Identifieur interne : 000409 ( Main/Exploration ); précédent : 000408; suivant : 000410Clinical and genetic features of cervical dystonia in a large multicenter cohort
Auteurs : Mark S. Ledoux ; Satya R. Vemula ; Jianfeng Xiao ; Misty M. Thompson ; Joel S. Perlmutter ; Laura J. Wright ; H. A. Jinnah ; Ami R. Rosen ; Peter Hedera ; Cynthia L. Comella ; Anne Weissbach ; Johanna Junker ; Joseph Jankovic [États-Unis] ; Richard L. Barbano ; Stephen G. Reich ; Ramon L. Rodriguez ; Brian D. Berman ; Sylvain Chouinard ; Lawrence Severt ; Pinky Agarwal ; Natividad P. StoverSource :
- Neurology: Genetics [ 2376-7839 ] ; 2016.
Abstract
To characterize the clinical and genetic features of cervical dystonia (CD).
Participants enrolled in the Dystonia Coalition biorepository (NCT01373424) with initial manifestation as CD were included in this study (n = 1,000). Data intake included demographics, family history, and the Global Dystonia Rating Scale. Participants were screened for sequence variants (SVs) in
The majority of participants were Caucasian (95%) and female (75%). The mean age at onset and disease duration were 45.5 ± 13.6 and 14.6 ± 11.8 years, respectively. At the time of assessment, 68.5% had involvement limited to the neck, shoulder(s), and proximal arm(s), whereas 47.4% had dystonia limited to the neck. The remaining 31.5% of the individuals exhibited more extensive anatomical spread. A head tremor was noted in 62% of the patients. Head tremor and laryngeal dystonia were more common in females. Psychiatric comorbidities, mainly depression and anxiety, were reported by 32% of the participants and were more common in females. Family histories of dystonia, parkinsonian disorder, and tremor were present in 14%, 11%, and 29% of the patients, respectively. Pathogenic or likely pathogenic SVs in
Head tremor, laryngeal dystonia, and psychiatric comorbidities are more common in female participants with CD. Coding and noncoding variants in
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DOI: 10.1212/NXG.0000000000000069
PubMed: 27123488
PubMed Central: 4830199
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Clinical and genetic features of cervical dystonia in a large multicenter cohort</title><author><name sortKey="Ledoux, Mark S" sort="Ledoux, Mark S" uniqKey="Ledoux M" first="Mark S." last="Ledoux">Mark S. Ledoux</name></author><author><name sortKey="Vemula, Satya R" sort="Vemula, Satya R" uniqKey="Vemula S" first="Satya R." last="Vemula">Satya R. Vemula</name></author><author><name sortKey="Xiao, Jianfeng" sort="Xiao, Jianfeng" uniqKey="Xiao J" first="Jianfeng" last="Xiao">Jianfeng Xiao</name></author><author><name sortKey="Thompson, Misty M" sort="Thompson, Misty M" uniqKey="Thompson M" first="Misty M." last="Thompson">Misty M. Thompson</name></author><author><name sortKey="Perlmutter, Joel S" sort="Perlmutter, Joel S" uniqKey="Perlmutter J" first="Joel S." last="Perlmutter">Joel S. Perlmutter</name></author><author><name sortKey="Wright, Laura J" sort="Wright, Laura J" uniqKey="Wright L" first="Laura J." last="Wright">Laura J. Wright</name></author><author><name sortKey="Jinnah, H A" sort="Jinnah, H A" uniqKey="Jinnah H" first="H. A." last="Jinnah">H. A. Jinnah</name></author><author><name sortKey="Rosen, Ami R" sort="Rosen, Ami R" uniqKey="Rosen A" first="Ami R." last="Rosen">Ami R. Rosen</name></author><author><name sortKey="Hedera, Peter" sort="Hedera, Peter" uniqKey="Hedera P" first="Peter" last="Hedera">Peter Hedera</name></author><author><name sortKey="Comella, Cynthia L" sort="Comella, Cynthia L" uniqKey="Comella C" first="Cynthia L." last="Comella">Cynthia L. Comella</name></author><author><name sortKey="Weissbach, Anne" sort="Weissbach, Anne" uniqKey="Weissbach A" first="Anne" last="Weissbach">Anne Weissbach</name></author><author><name sortKey="Junker, Johanna" sort="Junker, Johanna" uniqKey="Junker J" first="Johanna" last="Junker">Johanna Junker</name></author><author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name><affiliation><country>États-Unis</country><placeName><settlement type="city">Houston</settlement><region type="state">Texas</region></placeName><orgName type="university" n="3">Baylor College of Medicine</orgName></affiliation></author><author><name sortKey="Barbano, Richard L" sort="Barbano, Richard L" uniqKey="Barbano R" first="Richard L." last="Barbano">Richard L. Barbano</name></author><author><name sortKey="Reich, Stephen G" sort="Reich, Stephen G" uniqKey="Reich S" first="Stephen G." last="Reich">Stephen G. Reich</name></author><author><name sortKey="Rodriguez, Ramon L" sort="Rodriguez, Ramon L" uniqKey="Rodriguez R" first="Ramon L." last="Rodriguez">Ramon L. Rodriguez</name></author><author><name sortKey="Berman, Brian D" sort="Berman, Brian D" uniqKey="Berman B" first="Brian D." last="Berman">Brian D. Berman</name></author><author><name sortKey="Chouinard, Sylvain" sort="Chouinard, Sylvain" uniqKey="Chouinard S" first="Sylvain" last="Chouinard">Sylvain Chouinard</name></author><author><name sortKey="Severt, Lawrence" sort="Severt, Lawrence" uniqKey="Severt L" first="Lawrence" last="Severt">Lawrence Severt</name></author><author><name sortKey="Agarwal, Pinky" sort="Agarwal, Pinky" uniqKey="Agarwal P" first="Pinky" last="Agarwal">Pinky Agarwal</name></author><author><name sortKey="Stover, Natividad P" sort="Stover, Natividad P" uniqKey="Stover N" first="Natividad P." last="Stover">Natividad P. Stover</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27123488</idno><idno type="pmc">4830199</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830199</idno><idno type="RBID">PMC:4830199</idno><idno type="doi">10.1212/NXG.0000000000000069</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000A49</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A49</idno><idno type="wicri:Area/Pmc/Curation">000A49</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000A49</idno><idno type="wicri:Area/Pmc/Checkpoint">000149</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000149</idno><idno type="wicri:Area/Ncbi/Merge">001F56</idno><idno type="wicri:Area/Ncbi/Curation">001F56</idno><idno type="wicri:Area/Ncbi/Checkpoint">001F56</idno><idno type="wicri:Area/Main/Merge">000410</idno><idno type="wicri:Area/Main/Curation">000409</idno><idno type="wicri:Area/Main/Exploration">000409</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Clinical and genetic features of cervical dystonia in a large multicenter cohort</title><author><name sortKey="Ledoux, Mark S" sort="Ledoux, Mark S" uniqKey="Ledoux M" first="Mark S." last="Ledoux">Mark S. Ledoux</name></author><author><name sortKey="Vemula, Satya R" sort="Vemula, Satya R" uniqKey="Vemula S" first="Satya R." last="Vemula">Satya R. Vemula</name></author><author><name sortKey="Xiao, Jianfeng" sort="Xiao, Jianfeng" uniqKey="Xiao J" first="Jianfeng" last="Xiao">Jianfeng Xiao</name></author><author><name sortKey="Thompson, Misty M" sort="Thompson, Misty M" uniqKey="Thompson M" first="Misty M." last="Thompson">Misty M. Thompson</name></author><author><name sortKey="Perlmutter, Joel S" sort="Perlmutter, Joel S" uniqKey="Perlmutter J" first="Joel S." last="Perlmutter">Joel S. Perlmutter</name></author><author><name sortKey="Wright, Laura J" sort="Wright, Laura J" uniqKey="Wright L" first="Laura J." last="Wright">Laura J. Wright</name></author><author><name sortKey="Jinnah, H A" sort="Jinnah, H A" uniqKey="Jinnah H" first="H. A." last="Jinnah">H. A. Jinnah</name></author><author><name sortKey="Rosen, Ami R" sort="Rosen, Ami R" uniqKey="Rosen A" first="Ami R." last="Rosen">Ami R. Rosen</name></author><author><name sortKey="Hedera, Peter" sort="Hedera, Peter" uniqKey="Hedera P" first="Peter" last="Hedera">Peter Hedera</name></author><author><name sortKey="Comella, Cynthia L" sort="Comella, Cynthia L" uniqKey="Comella C" first="Cynthia L." last="Comella">Cynthia L. Comella</name></author><author><name sortKey="Weissbach, Anne" sort="Weissbach, Anne" uniqKey="Weissbach A" first="Anne" last="Weissbach">Anne Weissbach</name></author><author><name sortKey="Junker, Johanna" sort="Junker, Johanna" uniqKey="Junker J" first="Johanna" last="Junker">Johanna Junker</name></author><author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name><affiliation><country>États-Unis</country><placeName><settlement type="city">Houston</settlement><region type="state">Texas</region></placeName><orgName type="university" n="3">Baylor College of Medicine</orgName></affiliation></author><author><name sortKey="Barbano, Richard L" sort="Barbano, Richard L" uniqKey="Barbano R" first="Richard L." last="Barbano">Richard L. Barbano</name></author><author><name sortKey="Reich, Stephen G" sort="Reich, Stephen G" uniqKey="Reich S" first="Stephen G." last="Reich">Stephen G. Reich</name></author><author><name sortKey="Rodriguez, Ramon L" sort="Rodriguez, Ramon L" uniqKey="Rodriguez R" first="Ramon L." last="Rodriguez">Ramon L. Rodriguez</name></author><author><name sortKey="Berman, Brian D" sort="Berman, Brian D" uniqKey="Berman B" first="Brian D." last="Berman">Brian D. Berman</name></author><author><name sortKey="Chouinard, Sylvain" sort="Chouinard, Sylvain" uniqKey="Chouinard S" first="Sylvain" last="Chouinard">Sylvain Chouinard</name></author><author><name sortKey="Severt, Lawrence" sort="Severt, Lawrence" uniqKey="Severt L" first="Lawrence" last="Severt">Lawrence Severt</name></author><author><name sortKey="Agarwal, Pinky" sort="Agarwal, Pinky" uniqKey="Agarwal P" first="Pinky" last="Agarwal">Pinky Agarwal</name></author><author><name sortKey="Stover, Natividad P" sort="Stover, Natividad P" uniqKey="Stover N" first="Natividad P." last="Stover">Natividad P. Stover</name></author></analytic><series><title level="j">Neurology: Genetics</title><idno type="eISSN">2376-7839</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objective:</title><p>To characterize the clinical and genetic features of cervical dystonia (CD).</p></sec><sec><title>Methods:</title><p>Participants enrolled in the Dystonia Coalition biorepository (NCT01373424) with initial manifestation as CD were included in this study (n = 1,000). Data intake included demographics, family history, and the Global Dystonia Rating Scale. Participants were screened for sequence variants (SVs) in <italic>GNAL</italic>, <italic>THAP1</italic>, and Exon 5 of <italic>TOR1A</italic>.</p></sec><sec><title>Results:</title><p>The majority of participants were Caucasian (95%) and female (75%). The mean age at onset and disease duration were 45.5 ± 13.6 and 14.6 ± 11.8 years, respectively. At the time of assessment, 68.5% had involvement limited to the neck, shoulder(s), and proximal arm(s), whereas 47.4% had dystonia limited to the neck. The remaining 31.5% of the individuals exhibited more extensive anatomical spread. A head tremor was noted in 62% of the patients. Head tremor and laryngeal dystonia were more common in females. Psychiatric comorbidities, mainly depression and anxiety, were reported by 32% of the participants and were more common in females. Family histories of dystonia, parkinsonian disorder, and tremor were present in 14%, 11%, and 29% of the patients, respectively. Pathogenic or likely pathogenic SVs in <italic>THAP1</italic>, <italic>TOR1A</italic>, and <italic>GNAL</italic> were identified in 8 participants (0.8%). Two individuals harbored novel missense SVs in Exon 5 of <italic>TOR1A</italic>. Synonymous and noncoding SVs in <italic>THAP1</italic> and <italic>GNAL</italic> were identified in 4% of the cohort.</p></sec><sec><title>Conclusions:</title><p>Head tremor, laryngeal dystonia, and psychiatric comorbidities are more common in female participants with CD. Coding and noncoding variants in <italic>GNAL</italic>, <italic>THAP1</italic>, and <italic>TOR1A</italic> make small contributions to the pathogenesis of CD.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Defazio, G" uniqKey="Defazio G">G Defazio</name></author><author><name sortKey="Jankovic, J" uniqKey="Jankovic J">J Jankovic</name></author><author><name sortKey="Giel, Jl" uniqKey="Giel J">JL Giel</name></author><author><name sortKey="Papapetropoulos, S" uniqKey="Papapetropoulos S">S Papapetropoulos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Defazio, G" uniqKey="Defazio G">G Defazio</name></author><author><name sortKey="Abbruzzese, G" uniqKey="Abbruzzese G">G Abbruzzese</name></author><author><name sortKey="Livrea, P" uniqKey="Livrea P">P Livrea</name></author><author><name sortKey="Berardelli, A" uniqKey="Berardelli A">A 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sortKey="Gross, Re" uniqKey="Gross R">RE Gross</name></author><author><name sortKey="Lehericy, S" uniqKey="Lehericy S">S Lehericy</name></author><author><name sortKey="Hess, Ej" uniqKey="Hess E">EJ Hess</name></author><author><name sortKey="Jinnah, Ha" uniqKey="Jinnah H">HA Jinnah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, Ly" uniqKey="Ma L">LY Ma</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Yang, Ym" uniqKey="Yang Y">YM Yang</name></author><author><name sortKey="Feng, T" uniqKey="Feng T">T Feng</name></author><author><name sortKey="Wan, Xh" uniqKey="Wan X">XH Wan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vemula, Sr" uniqKey="Vemula S">SR Vemula</name></author><author><name sortKey="Xiao, J" uniqKey="Xiao J">J Xiao</name></author><author><name sortKey="Zhao, Y" uniqKey="Zhao Y">Y Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Calakos, N" uniqKey="Calakos N">N Calakos</name></author><author><name sortKey="Patel, Vd" uniqKey="Patel V">VD Patel</name></author><author><name sortKey="Gottron, M" uniqKey="Gottron M">M Gottron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zirn, B" uniqKey="Zirn B">B Zirn</name></author><author><name sortKey="Grundmann, K" uniqKey="Grundmann K">K Grundmann</name></author><author><name sortKey="Huppke, P" uniqKey="Huppke P">P Huppke</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Texas</li></region><settlement><li>Houston</li></settlement><orgName><li>Baylor College of Medicine</li></orgName></list><tree><noCountry><name sortKey="Agarwal, Pinky" sort="Agarwal, Pinky" uniqKey="Agarwal P" first="Pinky" last="Agarwal">Pinky Agarwal</name><name sortKey="Barbano, Richard L" sort="Barbano, Richard L" uniqKey="Barbano R" first="Richard L." last="Barbano">Richard L. Barbano</name><name sortKey="Berman, Brian D" sort="Berman, Brian D" uniqKey="Berman B" first="Brian D." last="Berman">Brian D. Berman</name><name sortKey="Chouinard, Sylvain" sort="Chouinard, Sylvain" uniqKey="Chouinard S" first="Sylvain" last="Chouinard">Sylvain Chouinard</name><name sortKey="Comella, Cynthia L" sort="Comella, Cynthia L" uniqKey="Comella C" first="Cynthia L." last="Comella">Cynthia L. Comella</name><name sortKey="Hedera, Peter" sort="Hedera, Peter" uniqKey="Hedera P" first="Peter" last="Hedera">Peter Hedera</name><name sortKey="Jinnah, H A" sort="Jinnah, H A" uniqKey="Jinnah H" first="H. A." last="Jinnah">H. A. Jinnah</name><name sortKey="Junker, Johanna" sort="Junker, Johanna" uniqKey="Junker J" first="Johanna" last="Junker">Johanna Junker</name><name sortKey="Ledoux, Mark S" sort="Ledoux, Mark S" uniqKey="Ledoux M" first="Mark S." last="Ledoux">Mark S. Ledoux</name><name sortKey="Perlmutter, Joel S" sort="Perlmutter, Joel S" uniqKey="Perlmutter J" first="Joel S." last="Perlmutter">Joel S. Perlmutter</name><name sortKey="Reich, Stephen G" sort="Reich, Stephen G" uniqKey="Reich S" first="Stephen G." last="Reich">Stephen G. Reich</name><name sortKey="Rodriguez, Ramon L" sort="Rodriguez, Ramon L" uniqKey="Rodriguez R" first="Ramon L." last="Rodriguez">Ramon L. Rodriguez</name><name sortKey="Rosen, Ami R" sort="Rosen, Ami R" uniqKey="Rosen A" first="Ami R." last="Rosen">Ami R. Rosen</name><name sortKey="Severt, Lawrence" sort="Severt, Lawrence" uniqKey="Severt L" first="Lawrence" last="Severt">Lawrence Severt</name><name sortKey="Stover, Natividad P" sort="Stover, Natividad P" uniqKey="Stover N" first="Natividad P." last="Stover">Natividad P. Stover</name><name sortKey="Thompson, Misty M" sort="Thompson, Misty M" uniqKey="Thompson M" first="Misty M." last="Thompson">Misty M. Thompson</name><name sortKey="Vemula, Satya R" sort="Vemula, Satya R" uniqKey="Vemula S" first="Satya R." last="Vemula">Satya R. Vemula</name><name sortKey="Weissbach, Anne" sort="Weissbach, Anne" uniqKey="Weissbach A" first="Anne" last="Weissbach">Anne Weissbach</name><name sortKey="Wright, Laura J" sort="Wright, Laura J" uniqKey="Wright L" first="Laura J." last="Wright">Laura J. Wright</name><name sortKey="Xiao, Jianfeng" sort="Xiao, Jianfeng" uniqKey="Xiao J" first="Jianfeng" last="Xiao">Jianfeng Xiao</name></noCountry><country name="États-Unis"><region name="Texas"><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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