Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset
Identifieur interne : 000180 ( Pmc/Checkpoint ); précédent : 000179; suivant : 000181Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset
Auteurs : W Nichols ; N. Pankratz ; D Marek ; M Pauciulo ; V Elsaesser ; C Halter ; A. Rudolph ; J. Wojcieszek ; R Pfeiffer ; T. ForoudSource :
- Neurology [ 0028-3878 ] ; 2009.
Abstract
To characterize sequence variation within the glucocerebrosidase (
We performed a comprehensive study of all
Nine different
This study suggests that
= confidence interval;
= Gaucher disease;
= Geriatric Depression Scale;
= Mini-Mental State Examination;
= National Cell Repository for Alzheimer’s Disease;
= nonparametric lod;
= odds ratio;
= Parkinson disease;
= Unified Parkinson’s Disease Rating Scale.
Url:
DOI: 10.1212/01.wnl.0000327823.81237.d1
PubMed: 18987351
PubMed Central: 2677501
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Mutations in <italic>GBA</italic> are associated with familial Parkinson disease susceptibility and age at onset</title><author><name sortKey="Nichols, W C" sort="Nichols, W C" uniqKey="Nichols W" first="W" last="Nichols">W Nichols</name></author><author><name sortKey="Pankratz, N" sort="Pankratz, N" uniqKey="Pankratz N" first="N" last="Pankratz">N. Pankratz</name></author><author><name sortKey="Marek, D K" sort="Marek, D K" uniqKey="Marek D" first="D" last="Marek">D Marek</name></author><author><name sortKey="Pauciulo, M W" sort="Pauciulo, M W" uniqKey="Pauciulo M" first="M" last="Pauciulo">M Pauciulo</name></author><author><name sortKey="Elsaesser, V E" sort="Elsaesser, V E" uniqKey="Elsaesser V" first="V" last="Elsaesser">V Elsaesser</name></author><author><name sortKey="Halter, C A" sort="Halter, C A" uniqKey="Halter C" first="C" last="Halter">C Halter</name></author><author><name sortKey="Rudolph, A" sort="Rudolph, A" uniqKey="Rudolph A" first="A" last="Rudolph">A. Rudolph</name></author><author><name sortKey="Wojcieszek, J" sort="Wojcieszek, J" uniqKey="Wojcieszek J" first="J" last="Wojcieszek">J. Wojcieszek</name></author><author><name sortKey="Pfeiffer, R F" sort="Pfeiffer, R F" uniqKey="Pfeiffer R" first="R" last="Pfeiffer">R Pfeiffer</name></author><author><name sortKey="Foroud, T" sort="Foroud, T" uniqKey="Foroud T" first="T" last="Foroud">T. Foroud</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18987351</idno><idno type="pmc">2677501</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677501</idno><idno type="RBID">PMC:2677501</idno><idno type="doi">10.1212/01.wnl.0000327823.81237.d1</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">000094</idno><idno type="wicri:Area/Pmc/Curation">000094</idno><idno type="wicri:Area/Pmc/Checkpoint">000180</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Mutations in <italic>GBA</italic> are associated with familial Parkinson disease susceptibility and age at onset</title><author><name sortKey="Nichols, W C" sort="Nichols, W C" uniqKey="Nichols W" first="W" last="Nichols">W Nichols</name></author><author><name sortKey="Pankratz, N" sort="Pankratz, N" uniqKey="Pankratz N" first="N" last="Pankratz">N. Pankratz</name></author><author><name sortKey="Marek, D K" sort="Marek, D K" uniqKey="Marek D" first="D" last="Marek">D Marek</name></author><author><name sortKey="Pauciulo, M W" sort="Pauciulo, M W" uniqKey="Pauciulo M" first="M" last="Pauciulo">M Pauciulo</name></author><author><name sortKey="Elsaesser, V E" sort="Elsaesser, V E" uniqKey="Elsaesser V" first="V" last="Elsaesser">V Elsaesser</name></author><author><name sortKey="Halter, C A" sort="Halter, C A" uniqKey="Halter C" first="C" last="Halter">C Halter</name></author><author><name sortKey="Rudolph, A" sort="Rudolph, A" uniqKey="Rudolph A" first="A" last="Rudolph">A. Rudolph</name></author><author><name sortKey="Wojcieszek, J" sort="Wojcieszek, J" uniqKey="Wojcieszek J" first="J" last="Wojcieszek">J. Wojcieszek</name></author><author><name sortKey="Pfeiffer, R F" sort="Pfeiffer, R F" uniqKey="Pfeiffer R" first="R" last="Pfeiffer">R Pfeiffer</name></author><author><name sortKey="Foroud, T" sort="Foroud, T" uniqKey="Foroud T" first="T" last="Foroud">T. Foroud</name></author></analytic><series><title level="j">Neurology</title><idno type="ISSN">0028-3878</idno><idno type="e-ISSN">1526-632X</idno><imprint><date when="2009">2009</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 sequence variation within the glucocerebrosidase (<italic>GBA</italic>) gene in a select subset of our sample of patients with familial Parkinson disease (PD) and then to test in our full sample whether these sequence variants increased the risk for PD and were associated with an earlier onset of disease.</p></sec><sec><title>Methods:</title><p>We performed a comprehensive study of all <italic>GBA</italic> exons in one patient with PD from each of 96 PD families, selected based on the family-specific lod scores at the <italic>GBA</italic> locus. Identified <italic>GBA</italic> variants were subsequently screened in all 1325 PD cases from 566 multiplex PD families and in 359 controls.</p></sec><sec><title>Results:</title><p>Nine different <italic>GBA</italic> variants, five previously reported, were identified in 21 of the 96 PD cases sequenced. Screening for these variants in the full sample identified 161 variant carriers (12.2%) in 99 different PD families. An unbiased estimate of the frequency of the five previously reported <italic>GBA</italic> variants in the familial PD sample was 12.6% and in the control sample was 5.3% (odds ratio 2.6; 95% confidence interval 1.5–4.4). Presence of a <italic>GBA</italic> variant was associated with an earlier age at onset (<italic>p</italic> = 0.0001). On average, those patients carrying a <italic>GBA</italic> variant had onset with PD 6.04 years earlier than those without a <italic>GBA</italic> variant.</p></sec><sec><title>Conclusions:</title><p>This study suggests that <italic>GBA</italic> is a susceptibility gene for familial Parkinson disease (PD) and patients with <italic>GBA</italic> variants have an earlier age at onset than patients with PD without <italic>GBA</italic> variants.</p></sec><sec><title>GLOSSARY</title><def-list list-type="abr"><def-item><term><bold>CI</bold></term><def><p> = confidence interval; </p></def></def-item><def-item><term><bold>GD</bold></term><def><p> = Gaucher disease; </p></def></def-item><def-item><term><bold>GDS</bold></term><def><p> = Geriatric Depression Scale; </p></def></def-item><def-item><term><bold>MMSE</bold></term><def><p> = Mini-Mental State Examination; </p></def></def-item><def-item><term><bold>NCRAD</bold></term><def><p> = National Cell Repository for Alzheimer’s Disease; </p></def></def-item><def-item><term><bold>NPL</bold></term><def><p> = nonparametric lod; </p></def></def-item><def-item><term><bold>OR</bold></term><def><p> = odds ratio; </p></def></def-item><def-item><term><bold>PD</bold></term><def><p> = Parkinson disease; </p></def></def-item><def-item><term><bold>UPDRS</bold></term><def><p> = Unified Parkinson’s Disease Rating Scale.</p></def></def-item></def-list></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Neurology</journal-id><journal-title>Neurology</journal-title><issn pub-type="ppub">0028-3878</issn><issn pub-type="epub">1526-632X</issn><publisher><publisher-name>American Academy of Neurology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18987351</article-id><article-id pub-id-type="pmc">2677501</article-id><article-id pub-id-type="publisher-id">znl00409000310</article-id><article-id pub-id-type="doi">10.1212/01.wnl.0000327823.81237.d1</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Mutations in <italic>GBA</italic> are associated with familial Parkinson disease susceptibility and age at onset</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Nichols</surname><given-names>W C.</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Pankratz</surname><given-names>N</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Marek</surname><given-names>D K.</given-names></name><degrees>BS</degrees></contrib><contrib contrib-type="author"><name><surname>Pauciulo</surname><given-names>M W.</given-names></name><degrees>MBA</degrees></contrib><contrib contrib-type="author"><name><surname>Elsaesser</surname><given-names>V E.</given-names></name><degrees>BS</degrees></contrib><contrib contrib-type="author"><name><surname>Halter</surname><given-names>C A.</given-names></name><degrees>MS</degrees></contrib><contrib contrib-type="author"><name><surname>Rudolph</surname><given-names>A</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Wojcieszek</surname><given-names>J</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Pfeiffer</surname><given-names>R F.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Foroud</surname><given-names>T</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><collab>For the Parkinson Study Group–PROGENI Investigators</collab><xref ref-type="aff" rid="N0x1d248d0N0x2b7eb08">*</xref></contrib></contrib-group><aff id="N0x1d248d0N0x2b7eb08">From Cincinnati Children’s Hospital Medical Center (W.C.N., D.K.M., M.W.P., V.E.E.), OH; University of Cincinnati School of Medicine (W.C.N.), OH; Indiana University Medical Center (N.P., C.A.H., J.W., T.F.), Indianapolis; University of Rochester (A.R.), NY; and University of Tennessee Health Science Center (R.F.P.), Memphis.<break></break></aff><pub-date pub-type="ppub"><day>27</day><month>1</month><year>2009</year></pub-date><volume>72</volume><issue>4</issue><fpage>310</fpage><lpage>316</lpage><copyright-statement>Copyright © 2009 by AAN Enterprises, Inc.</copyright-statement><abstract><sec><title>Objective:</title><p>To characterize sequence variation within the glucocerebrosidase (<italic>GBA</italic>) gene in a select subset of our sample of patients with familial Parkinson disease (PD) and then to test in our full sample whether these sequence variants increased the risk for PD and were associated with an earlier onset of disease.</p></sec><sec><title>Methods:</title><p>We performed a comprehensive study of all <italic>GBA</italic> exons in one patient with PD from each of 96 PD families, selected based on the family-specific lod scores at the <italic>GBA</italic> locus. Identified <italic>GBA</italic> variants were subsequently screened in all 1325 PD cases from 566 multiplex PD families and in 359 controls.</p></sec><sec><title>Results:</title><p>Nine different <italic>GBA</italic> variants, five previously reported, were identified in 21 of the 96 PD cases sequenced. Screening for these variants in the full sample identified 161 variant carriers (12.2%) in 99 different PD families. An unbiased estimate of the frequency of the five previously reported <italic>GBA</italic> variants in the familial PD sample was 12.6% and in the control sample was 5.3% (odds ratio 2.6; 95% confidence interval 1.5–4.4). Presence of a <italic>GBA</italic> variant was associated with an earlier age at onset (<italic>p</italic> = 0.0001). On average, those patients carrying a <italic>GBA</italic> variant had onset with PD 6.04 years earlier than those without a <italic>GBA</italic> variant.</p></sec><sec><title>Conclusions:</title><p>This study suggests that <italic>GBA</italic> is a susceptibility gene for familial Parkinson disease (PD) and patients with <italic>GBA</italic> variants have an earlier age at onset than patients with PD without <italic>GBA</italic> variants.</p></sec><sec><title>GLOSSARY</title><def-list list-type="abr"><def-item><term><bold>CI</bold></term><def><p> = confidence interval; </p></def></def-item><def-item><term><bold>GD</bold></term><def><p> = Gaucher disease; </p></def></def-item><def-item><term><bold>GDS</bold></term><def><p> = Geriatric Depression Scale; </p></def></def-item><def-item><term><bold>MMSE</bold></term><def><p> = Mini-Mental State Examination; </p></def></def-item><def-item><term><bold>NCRAD</bold></term><def><p> = National Cell Repository for Alzheimer’s Disease; </p></def></def-item><def-item><term><bold>NPL</bold></term><def><p> = nonparametric lod; </p></def></def-item><def-item><term><bold>OR</bold></term><def><p> = odds ratio; </p></def></def-item><def-item><term><bold>PD</bold></term><def><p> = Parkinson disease; </p></def></def-item><def-item><term><bold>UPDRS</bold></term><def><p> = Unified Parkinson’s Disease Rating Scale.</p></def></def-item></def-list></sec></abstract></article-meta><notes><p>Address correspondence and reprint requests to Dr. William C. Nichols, Associate Professor of Pediatrics, Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 <email>bill.nichols@cchmc.org</email></p><p>Supplemental data at <ext-link ext-link-type="uri" xlink:href="www.neurology.org">www.neurology.org</ext-link></p><p><italic>e-Pub ahead of print on November 5, 2008, at</italic> <ext-link ext-link-type="uri" xlink:href="www.neurology.org">www.neurology.org</ext-link>.</p><p>*The Parkinson Study Group–PROGENI Investigators are listed in the appendix.</p><p>Supported by R01 NS37167, MO1 RR-00750, and the National Cell Repository for Alzheimer’s Disease (U24 AG021886). This study used samples and clinical data from the National Institute of Neurological Disorders and Stroke Human Genetics Resource Center DNA and Cell Line Repository (<ext-link ext-link-type="uri" xlink:href="http://ccr.coriell.org/ninds">http://ccr.coriell.org/ninds</ext-link>).</p><p><italic>Disclosure:</italic> The authors report no disclosures.</p><p>Received February 26, 2008. Accepted in final form July 2, 2008.</p></notes></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Elsaesser, V E" sort="Elsaesser, V E" uniqKey="Elsaesser V" first="V" last="Elsaesser">V Elsaesser</name><name sortKey="Foroud, T" sort="Foroud, T" uniqKey="Foroud T" first="T" last="Foroud">T. Foroud</name><name sortKey="Halter, C A" sort="Halter, C A" uniqKey="Halter C" first="C" last="Halter">C Halter</name><name sortKey="Marek, D K" sort="Marek, D K" uniqKey="Marek D" first="D" last="Marek">D Marek</name><name sortKey="Nichols, W C" sort="Nichols, W C" uniqKey="Nichols W" first="W" last="Nichols">W Nichols</name><name sortKey="Pankratz, N" sort="Pankratz, N" uniqKey="Pankratz N" first="N" last="Pankratz">N. Pankratz</name><name sortKey="Pauciulo, M W" sort="Pauciulo, M W" uniqKey="Pauciulo M" first="M" last="Pauciulo">M Pauciulo</name><name sortKey="Pfeiffer, R F" sort="Pfeiffer, R F" uniqKey="Pfeiffer R" first="R" last="Pfeiffer">R Pfeiffer</name><name sortKey="Rudolph, A" sort="Rudolph, A" uniqKey="Rudolph A" first="A" last="Rudolph">A. Rudolph</name><name sortKey="Wojcieszek, J" sort="Wojcieszek, J" uniqKey="Wojcieszek J" first="J" last="Wojcieszek">J. Wojcieszek</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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