Phenotypic and molecular analyses of primary lateral sclerosis
Identifieur interne : 000589 ( Main/Exploration ); précédent : 000588; suivant : 000590Phenotypic and molecular analyses of primary lateral sclerosis
Auteurs : Hiroshi Mitsumoto ; Peter L. Nagy ; Chris Gennings ; Jennifer Murphy ; Howard Andrews ; Raymond Goetz ; Mary Kay Floeter ; Jonathan Hupf ; Jessica Singleton ; Richard J. Barohn ; Sharon Nations ; Christen Shoesmith ; Edward Kasarskis ; Pam Factor-LitvakSource :
- Neurology: Genetics [ 2376-7839 ] ; 2015.
Abstract
To understand phenotypic and molecular characteristics of patients with clinically “definite” primary lateral sclerosis (PLS) in a prospective study.
Six sites enrolled 41 patients who had pure upper motor neuron dysfunction, bulbar symptoms, a normal EMG done within 12 months of enrollment, and onset of symptoms ≥5 years before enrollment. For phenotypic analyses, 27 demographic, clinical, and cognitive variables were analyzed using the k-means clustering method. For molecular studies, 34 available DNA samples were tested for the
K-means clustering using the 25 patients with complete datasets suggested that patients with PLS can be classified into 2 groups based on clinical variables, namely dysphagia, objective bulbar signs, and urinary urgency. Secondary analyses performed in all 41 patients and including only variables with complete data corroborated the results from the primary analysis. We found no evidence that neurocognitive variables are important in classifying patients with PLS. Molecular studies identified
Cluster analyses based on clinical variables indicated at least 2 subgroups of clinically definite PLS. Molecular analyses further identified 4 cases with mutations associated with amyotrophic lateral sclerosis, Parkinson disease, and possibly hereditary spastic paraplegia. Phenotypic and molecular characterization is the first step in investigating biological clues toward the definition of PLS. Further studies with larger numbers of patients are essential.
Url:
DOI: 10.1212/01.NXG.0000464294.88607.dd
PubMed: 27066542
PubMed Central: 4821084
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Phenotypic and molecular analyses of primary lateral sclerosis</title><author><name sortKey="Mitsumoto, Hiroshi" sort="Mitsumoto, Hiroshi" uniqKey="Mitsumoto H" first="Hiroshi" last="Mitsumoto">Hiroshi Mitsumoto</name></author><author><name sortKey="Nagy, Peter L" sort="Nagy, Peter L" uniqKey="Nagy P" first="Peter L." last="Nagy">Peter L. Nagy</name></author><author><name sortKey="Gennings, Chris" sort="Gennings, Chris" uniqKey="Gennings C" first="Chris" last="Gennings">Chris Gennings</name></author><author><name sortKey="Murphy, Jennifer" sort="Murphy, Jennifer" uniqKey="Murphy J" first="Jennifer" last="Murphy">Jennifer Murphy</name></author><author><name sortKey="Andrews, Howard" sort="Andrews, Howard" uniqKey="Andrews H" first="Howard" last="Andrews">Howard Andrews</name></author><author><name sortKey="Goetz, Raymond" sort="Goetz, Raymond" uniqKey="Goetz R" first="Raymond" last="Goetz">Raymond Goetz</name></author><author><name sortKey="Floeter, Mary Kay" sort="Floeter, Mary Kay" uniqKey="Floeter M" first="Mary Kay" last="Floeter">Mary Kay Floeter</name></author><author><name sortKey="Hupf, Jonathan" sort="Hupf, Jonathan" uniqKey="Hupf J" first="Jonathan" last="Hupf">Jonathan Hupf</name></author><author><name sortKey="Singleton, Jessica" sort="Singleton, Jessica" uniqKey="Singleton J" first="Jessica" last="Singleton">Jessica Singleton</name></author><author><name sortKey="Barohn, Richard J" sort="Barohn, Richard J" uniqKey="Barohn R" first="Richard J." last="Barohn">Richard J. Barohn</name></author><author><name sortKey="Nations, Sharon" sort="Nations, Sharon" uniqKey="Nations S" first="Sharon" last="Nations">Sharon Nations</name></author><author><name sortKey="Shoesmith, Christen" sort="Shoesmith, Christen" uniqKey="Shoesmith C" first="Christen" last="Shoesmith">Christen Shoesmith</name></author><author><name sortKey="Kasarskis, Edward" sort="Kasarskis, Edward" uniqKey="Kasarskis E" first="Edward" last="Kasarskis">Edward Kasarskis</name></author><author><name sortKey="Factor Litvak, Pam" sort="Factor Litvak, Pam" uniqKey="Factor Litvak P" first="Pam" last="Factor-Litvak">Pam Factor-Litvak</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27066542</idno><idno type="pmc">4821084</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821084</idno><idno type="RBID">PMC:4821084</idno><idno type="doi">10.1212/01.NXG.0000464294.88607.dd</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000A48</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A48</idno><idno type="wicri:Area/Pmc/Curation">000A48</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000A48</idno><idno type="wicri:Area/Pmc/Checkpoint">000235</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000235</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">000523</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000523</idno><idno type="wicri:Area/PubMed/Curation">000523</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000523</idno><idno type="wicri:Area/PubMed/Checkpoint">000523</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000523</idno><idno type="wicri:Area/Ncbi/Merge">001F32</idno><idno type="wicri:Area/Ncbi/Curation">001F32</idno><idno type="wicri:Area/Ncbi/Checkpoint">001F32</idno><idno type="wicri:Area/Main/Merge">000590</idno><idno type="wicri:Area/Main/Curation">000589</idno><idno type="wicri:Area/Main/Exploration">000589</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Phenotypic and molecular analyses of primary lateral sclerosis</title><author><name sortKey="Mitsumoto, Hiroshi" sort="Mitsumoto, Hiroshi" uniqKey="Mitsumoto H" first="Hiroshi" last="Mitsumoto">Hiroshi Mitsumoto</name></author><author><name sortKey="Nagy, Peter L" sort="Nagy, Peter L" uniqKey="Nagy P" first="Peter L." last="Nagy">Peter L. Nagy</name></author><author><name sortKey="Gennings, Chris" sort="Gennings, Chris" uniqKey="Gennings C" first="Chris" last="Gennings">Chris Gennings</name></author><author><name sortKey="Murphy, Jennifer" sort="Murphy, Jennifer" uniqKey="Murphy J" first="Jennifer" last="Murphy">Jennifer Murphy</name></author><author><name sortKey="Andrews, Howard" sort="Andrews, Howard" uniqKey="Andrews H" first="Howard" last="Andrews">Howard Andrews</name></author><author><name sortKey="Goetz, Raymond" sort="Goetz, Raymond" uniqKey="Goetz R" first="Raymond" last="Goetz">Raymond Goetz</name></author><author><name sortKey="Floeter, Mary Kay" sort="Floeter, Mary Kay" uniqKey="Floeter M" first="Mary Kay" last="Floeter">Mary Kay Floeter</name></author><author><name sortKey="Hupf, Jonathan" sort="Hupf, Jonathan" uniqKey="Hupf J" first="Jonathan" last="Hupf">Jonathan Hupf</name></author><author><name sortKey="Singleton, Jessica" sort="Singleton, Jessica" uniqKey="Singleton J" first="Jessica" last="Singleton">Jessica Singleton</name></author><author><name sortKey="Barohn, Richard J" sort="Barohn, Richard J" uniqKey="Barohn R" first="Richard J." last="Barohn">Richard J. Barohn</name></author><author><name sortKey="Nations, Sharon" sort="Nations, Sharon" uniqKey="Nations S" first="Sharon" last="Nations">Sharon Nations</name></author><author><name sortKey="Shoesmith, Christen" sort="Shoesmith, Christen" uniqKey="Shoesmith C" first="Christen" last="Shoesmith">Christen Shoesmith</name></author><author><name sortKey="Kasarskis, Edward" sort="Kasarskis, Edward" uniqKey="Kasarskis E" first="Edward" last="Kasarskis">Edward Kasarskis</name></author><author><name sortKey="Factor Litvak, Pam" sort="Factor Litvak, Pam" uniqKey="Factor Litvak P" first="Pam" last="Factor-Litvak">Pam Factor-Litvak</name></author></analytic><series><title level="j">Neurology: Genetics</title><idno type="eISSN">2376-7839</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objective:</title><p>To understand phenotypic and molecular characteristics of patients with clinically “definite” primary lateral sclerosis (PLS) in a prospective study.</p></sec><sec><title>Methods:</title><p>Six sites enrolled 41 patients who had pure upper motor neuron dysfunction, bulbar symptoms, a normal EMG done within 12 months of enrollment, and onset of symptoms ≥5 years before enrollment. For phenotypic analyses, 27 demographic, clinical, and cognitive variables were analyzed using the k-means clustering method. For molecular studies, 34 available DNA samples were tested for the <italic>C9ORF72</italic> mutation, and exome sequencing was performed to exclude other neurologic diseases with known genetic cause.</p></sec><sec><title>Results:</title><p>K-means clustering using the 25 patients with complete datasets suggested that patients with PLS can be classified into 2 groups based on clinical variables, namely dysphagia, objective bulbar signs, and urinary urgency. Secondary analyses performed in all 41 patients and including only variables with complete data corroborated the results from the primary analysis. We found no evidence that neurocognitive variables are important in classifying patients with PLS. Molecular studies identified <italic>C9ORF72</italic> expansion in one patient. Well-characterized pathogenic mutations were identified in <italic>SPG7, DCTN1</italic>, and <italic>PARK2</italic>. Most cases showed no known relevant mutations.</p></sec><sec><title>Conclusions:</title><p>Cluster analyses based on clinical variables indicated at least 2 subgroups of clinically definite PLS. Molecular analyses further identified 4 cases with mutations associated with amyotrophic lateral sclerosis, Parkinson disease, and possibly hereditary spastic paraplegia. Phenotypic and molecular characterization is the first step in investigating biological clues toward the definition of PLS. 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uniqKey="Whittle A">AJ Whittle</name></author><author><name sortKey="Ross, Oa" uniqKey="Ross O">OA Ross</name></author><author><name sortKey="Naini, A" uniqKey="Naini A">A Naini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vilarino Guell, C" uniqKey="Vilarino Guell C">C Vilarino-Guell</name></author><author><name sortKey="Wider, C" uniqKey="Wider C">C Wider</name></author><author><name sortKey="Soto Ortolaza, Ai" uniqKey="Soto Ortolaza A">AI Soto-Ortolaza</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Andrews, Howard" sort="Andrews, Howard" uniqKey="Andrews H" first="Howard" last="Andrews">Howard Andrews</name><name sortKey="Barohn, Richard J" sort="Barohn, Richard J" uniqKey="Barohn R" first="Richard J." last="Barohn">Richard J. Barohn</name><name sortKey="Factor Litvak, Pam" sort="Factor Litvak, Pam" uniqKey="Factor Litvak P" first="Pam" last="Factor-Litvak">Pam Factor-Litvak</name><name sortKey="Floeter, Mary Kay" sort="Floeter, Mary Kay" uniqKey="Floeter M" first="Mary Kay" last="Floeter">Mary Kay Floeter</name><name sortKey="Gennings, Chris" sort="Gennings, Chris" uniqKey="Gennings C" first="Chris" last="Gennings">Chris Gennings</name><name sortKey="Goetz, Raymond" sort="Goetz, Raymond" uniqKey="Goetz R" first="Raymond" last="Goetz">Raymond Goetz</name><name sortKey="Hupf, Jonathan" sort="Hupf, Jonathan" uniqKey="Hupf J" first="Jonathan" last="Hupf">Jonathan Hupf</name><name sortKey="Kasarskis, Edward" sort="Kasarskis, Edward" uniqKey="Kasarskis E" first="Edward" last="Kasarskis">Edward Kasarskis</name><name sortKey="Mitsumoto, Hiroshi" sort="Mitsumoto, Hiroshi" uniqKey="Mitsumoto H" first="Hiroshi" last="Mitsumoto">Hiroshi Mitsumoto</name><name sortKey="Murphy, Jennifer" sort="Murphy, Jennifer" uniqKey="Murphy J" first="Jennifer" last="Murphy">Jennifer Murphy</name><name sortKey="Nagy, Peter L" sort="Nagy, Peter L" uniqKey="Nagy P" first="Peter L." last="Nagy">Peter L. Nagy</name><name sortKey="Nations, Sharon" sort="Nations, Sharon" uniqKey="Nations S" first="Sharon" last="Nations">Sharon Nations</name><name sortKey="Shoesmith, Christen" sort="Shoesmith, Christen" uniqKey="Shoesmith C" first="Christen" last="Shoesmith">Christen Shoesmith</name><name sortKey="Singleton, Jessica" sort="Singleton, Jessica" uniqKey="Singleton J" first="Jessica" last="Singleton">Jessica Singleton</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Phenotypic and molecular analyses of primary lateral sclerosis
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