Serveur d'exploration sur la maladie de Parkinson

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Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis

Identifieur interne : 000670 ( Main/Curation ); précédent : 000669; suivant : 000671

Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis

Auteurs : Michael A. Van Es [Pays-Bas] ; Helenius J. Schelhaas [Pays-Bas] ; Paul W. J. Van Vught [Pays-Bas] ; Nicola Ticozzi [États-Unis, Italie] ; Peter M. Andersen [Suède] ; Ewout J. N. Groen [Pays-Bas] ; Claudia Schulte [Allemagne] ; Hylke M. Blauw [Pays-Bas] ; Max Koppers [Pays-Bas] ; Frank P. Diekstra [Pays-Bas] ; Katsumi Fumoto [Pays-Bas] ; Ashley Lyn Leclerc [États-Unis] ; Pamela Keagle [États-Unis] ; Bastiaan R. Bloem [Pays-Bas] ; Hans Scheffer [Pays-Bas] ; Bart F. L. Van Nuenen [Pays-Bas] ; Marka Van Blitterswijk [Pays-Bas] ; Wouter Van Rheenen [Pays-Bas] ; Anne-Marie Wills [États-Unis] ; Patrick P. Lowe [États-Unis] ; Guo-Fu Hu [États-Unis] ; Wenhao Yu [États-Unis] ; Hiroko Kishikawa [États-Unis] ; David Wu [États-Unis] ; Rebecca D. Folkerth [États-Unis] ; Claudio Mariani [Italie] ; Stefano Goldwurm [Italie] ; Gianni Pezzoli [Italie] ; Philip Van Damme [Belgique] ; Robin Lemmens [Belgique] ; Caroline Dahlberg [Suède] ; Anna Birve [Suède] ; Rubén Fernández-Santiago [Pays-Bas, Espagne, Allemagne] ; Stefan Waibel [Allemagne] ; Christine Klein [Allemagne] ; Markus Weber [Suisse] ; Anneke J. Van Der Kooi [Pays-Bas] ; Marianne De Visser [Pays-Bas] ; Dagmar Verbaan [Pays-Bas] ; Jacobus J. Van Hilten [Pays-Bas] ; Peter Heutink [Pays-Bas] ; Eric A. M. Hennekam [Pays-Bas] ; Edwin Cuppen [Pays-Bas] ; Daniela Berg [Pays-Bas] ; Robert H. Brown Jr [États-Unis] ; Vincenzo Silani [Italie] ; Thomas Gasser [Allemagne] ; Albert C. Ludolph [Allemagne] ; Wim Robberecht [Belgique] ; Roel A. Ophoff [Pays-Bas, États-Unis] ; Jan H. Veldink [Pays-Bas] ; R. Jeroen Pasterkamp [Pays-Bas] ; Paul I. W. De Bakker [Pays-Bas, États-Unis] ; John E. Landers [États-Unis] ; Bart P. Van De Warrenburg [Pays-Bas] ; Leonard H. Van Den Berg [Pays-Bas]

Source :

RBID : ISTEX:1104402D2CD5B78610B101FB2326A7D93EC038A3

Abstract

Objective:: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. Methods:: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel‐Haenszel procedure was used to estimate odds ratios. Results:: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10−6 for ALS and p = 4.3 × 10−5 for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. Interpretation:: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD. ANN NEUROL 2011;70:964–973

Url:
DOI: 10.1002/ana.22611

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ISTEX:1104402D2CD5B78610B101FB2326A7D93EC038A3

Le document en format XML

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<name sortKey="Scheffer, Hans" sort="Scheffer, Hans" uniqKey="Scheffer H" first="Hans" last="Scheffer">Hans Scheffer</name>
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<name sortKey="Van Blitterswijk, Marka" sort="Van Blitterswijk, Marka" uniqKey="Van Blitterswijk M" first="Marka" last="Van Blitterswijk">Marka Van Blitterswijk</name>
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<name sortKey="Wills, Anne Arie" sort="Wills, Anne Arie" uniqKey="Wills A" first="Anne-Marie" last="Wills">Anne-Marie Wills</name>
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<name sortKey="Lowe, Patrick P" sort="Lowe, Patrick P" uniqKey="Lowe P" first="Patrick P." last="Lowe">Patrick P. Lowe</name>
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<name sortKey="Hu, Guo U" sort="Hu, Guo U" uniqKey="Hu G" first="Guo-Fu" last="Hu">Guo-Fu Hu</name>
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<name sortKey="Yu, Wenhao" sort="Yu, Wenhao" uniqKey="Yu W" first="Wenhao" last="Yu">Wenhao Yu</name>
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<region type="state">Massachusetts</region>
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<name sortKey="Kishikawa, Hiroko" sort="Kishikawa, Hiroko" uniqKey="Kishikawa H" first="Hiroko" last="Kishikawa">Hiroko Kishikawa</name>
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<name sortKey="Wu, David" sort="Wu, David" uniqKey="Wu D" first="David" last="Wu">David Wu</name>
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<mods:affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</mods:affiliation>
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<region type="state">Massachusetts</region>
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<name sortKey="Mariani, Claudio" sort="Mariani, Claudio" uniqKey="Mariani C" first="Claudio" last="Mariani">Claudio Mariani</name>
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<name sortKey="Goldwurm, Stefano" sort="Goldwurm, Stefano" uniqKey="Goldwurm S" first="Stefano" last="Goldwurm">Stefano Goldwurm</name>
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<name sortKey="Van Damme, Philip" sort="Van Damme, Philip" uniqKey="Van Damme P" first="Philip" last="Van Damme">Philip Van Damme</name>
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<mods:affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</mods:affiliation>
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<wicri:regionArea>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven</wicri:regionArea>
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<name sortKey="Lemmens, Robin" sort="Lemmens, Robin" uniqKey="Lemmens R" first="Robin" last="Lemmens">Robin Lemmens</name>
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<mods:affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</mods:affiliation>
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<wicri:regionArea>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven</wicri:regionArea>
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<name sortKey="Dahlberg, Caroline" sort="Dahlberg, Caroline" uniqKey="Dahlberg C" first="Caroline" last="Dahlberg">Caroline Dahlberg</name>
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<name sortKey="Birve, Anna" sort="Birve, Anna" uniqKey="Birve A" first="Anna" last="Birve">Anna Birve</name>
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<mods:affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</mods:affiliation>
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<name sortKey="Fernandez Antiago, Ruben" sort="Fernandez Antiago, Ruben" uniqKey="Fernandez Antiago R" first="Rubén" last="Fernández-Santiago">Rubén Fernández-Santiago</name>
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<wicri:regionArea>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht</wicri:regionArea>
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<mods:affiliation>Department for Clinical and Experimental Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Barcelona, Spain</mods:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department for Clinical and Experimental Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Barcelona</wicri:regionArea>
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<affiliation wicri:level="1">
<mods:affiliation>Graduate School of Cellular and Molecular Neuroscience, International Max Planck Research School, Graduate Training Center of Neuroscience, Eberhard‐Karls University, Tübingen, Germany</mods:affiliation>
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<mods:affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation>
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<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
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<name sortKey="Veldink, Jan H" sort="Veldink, Jan H" uniqKey="Veldink J" first="Jan H." last="Veldink">Jan H. Veldink</name>
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<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
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<name sortKey="Pasterkamp, R Jeroen" sort="Pasterkamp, R Jeroen" uniqKey="Pasterkamp R" first="R. Jeroen" last="Pasterkamp">R. Jeroen Pasterkamp</name>
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<mods:affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation>
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<name sortKey="De Bakker, Paul I W" sort="De Bakker, Paul I W" uniqKey="De Bakker P" first="Paul I. W." last="De Bakker">Paul I. W. De Bakker</name>
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<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
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<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
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<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
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<title level="a" type="main" xml:lang="en">Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis</title>
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<name sortKey="Van Es, Michael A" sort="Van Es, Michael A" uniqKey="Van Es M" first="Michael A." last="Van Es">Michael A. Van Es</name>
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<mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht</wicri:regionArea>
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<name sortKey="Schelhaas, Helenius J" sort="Schelhaas, Helenius J" uniqKey="Schelhaas H" first="Helenius J." last="Schelhaas">Helenius J. Schelhaas</name>
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<mods:affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
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<name sortKey="Van Vught, Paul W J" sort="Van Vught, Paul W J" uniqKey="Van Vught P" first="Paul W. J." last="Van Vught">Paul W. J. Van Vught</name>
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<country xml:lang="fr">États-Unis</country>
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<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
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<name sortKey="Leclerc, Ashley Lyn" sort="Leclerc, Ashley Lyn" uniqKey="Leclerc A" first="Ashley Lyn" last="Leclerc">Ashley Lyn Leclerc</name>
<affiliation wicri:level="2">
<mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Neurology, University of Massachusetts Medical School, Worcester</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Keagle, Pamela" sort="Keagle, Pamela" uniqKey="Keagle P" first="Pamela" last="Keagle">Pamela Keagle</name>
<affiliation wicri:level="2">
<mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Neurology, University of Massachusetts Medical School, Worcester</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Bloem, Bastiaan R" sort="Bloem, Bastiaan R" uniqKey="Bloem B" first="Bastiaan R." last="Bloem">Bastiaan R. Bloem</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Scheffer, Hans" sort="Scheffer, Hans" uniqKey="Scheffer H" first="Hans" last="Scheffer">Hans Scheffer</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Human Genetics, Radboud University Medical Center, Nijmegen</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Van Nuenen, Bart F L" sort="Van Nuenen, Bart F L" uniqKey="Van Nuenen B" first="Bart F. L." last="Van Nuenen">Bart F. L. Van Nuenen</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Van Blitterswijk, Marka" sort="Van Blitterswijk, Marka" uniqKey="Van Blitterswijk M" first="Marka" last="Van Blitterswijk">Marka Van Blitterswijk</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Van Rheenen, Wouter" sort="Van Rheenen, Wouter" uniqKey="Van Rheenen W" first="Wouter" last="Van Rheenen">Wouter Van Rheenen</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wills, Anne Arie" sort="Wills, Anne Arie" uniqKey="Wills A" first="Anne-Marie" last="Wills">Anne-Marie Wills</name>
<affiliation wicri:level="2">
<mods:affiliation>Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Lowe, Patrick P" sort="Lowe, Patrick P" uniqKey="Lowe P" first="Patrick P." last="Lowe">Patrick P. Lowe</name>
<affiliation wicri:level="2">
<mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Neurology, University of Massachusetts Medical School, Worcester</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Hu, Guo U" sort="Hu, Guo U" uniqKey="Hu G" first="Guo-Fu" last="Hu">Guo-Fu Hu</name>
<affiliation wicri:level="2">
<mods:affiliation>Department of Pathology, Harvard Medical School, Boston, MA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Pathology, Harvard Medical School, Boston</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Yu, Wenhao" sort="Yu, Wenhao" uniqKey="Yu W" first="Wenhao" last="Yu">Wenhao Yu</name>
<affiliation wicri:level="2">
<mods:affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Pathology, Brigham and Women's Hospital, Boston</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Kishikawa, Hiroko" sort="Kishikawa, Hiroko" uniqKey="Kishikawa H" first="Hiroko" last="Kishikawa">Hiroko Kishikawa</name>
<affiliation wicri:level="2">
<mods:affiliation>Department of Pathology, Harvard Medical School, Boston, MA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Pathology, Harvard Medical School, Boston</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Wu, David" sort="Wu, David" uniqKey="Wu D" first="David" last="Wu">David Wu</name>
<affiliation wicri:level="2">
<mods:affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Pathology, Brigham and Women's Hospital, Boston</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Folkerth, Rebecca D" sort="Folkerth, Rebecca D" uniqKey="Folkerth R" first="Rebecca D." last="Folkerth">Rebecca D. Folkerth</name>
<affiliation wicri:level="2">
<mods:affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Pathology, Brigham and Women's Hospital, Boston</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Mariani, Claudio" sort="Mariani, Claudio" uniqKey="Mariani C" first="Claudio" last="Mariani">Claudio Mariani</name>
<affiliation wicri:level="1">
<mods:affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</mods:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Goldwurm, Stefano" sort="Goldwurm, Stefano" uniqKey="Goldwurm S" first="Stefano" last="Goldwurm">Stefano Goldwurm</name>
<affiliation wicri:level="1">
<mods:affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</mods:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Pezzoli, Gianni" sort="Pezzoli, Gianni" uniqKey="Pezzoli G" first="Gianni" last="Pezzoli">Gianni Pezzoli</name>
<affiliation wicri:level="1">
<mods:affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</mods:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Van Damme, Philip" sort="Van Damme, Philip" uniqKey="Van Damme P" first="Philip" last="Van Damme">Philip Van Damme</name>
<affiliation wicri:level="1">
<mods:affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</mods:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Experimental Neurology, University of Leuven, Leuven</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<mods:affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</mods:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</mods:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lemmens, Robin" sort="Lemmens, Robin" uniqKey="Lemmens R" first="Robin" last="Lemmens">Robin Lemmens</name>
<affiliation wicri:level="1">
<mods:affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</mods:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Experimental Neurology, University of Leuven, Leuven</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<mods:affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</mods:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</mods:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Dahlberg, Caroline" sort="Dahlberg, Caroline" uniqKey="Dahlberg C" first="Caroline" last="Dahlberg">Caroline Dahlberg</name>
<affiliation wicri:level="1">
<mods:affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</mods:affiliation>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Birve, Anna" sort="Birve, Anna" uniqKey="Birve A" first="Anna" last="Birve">Anna Birve</name>
<affiliation wicri:level="1">
<mods:affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</mods:affiliation>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Fernandez Antiago, Ruben" sort="Fernandez Antiago, Ruben" uniqKey="Fernandez Antiago R" first="Rubén" last="Fernández-Santiago">Rubén Fernández-Santiago</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<mods:affiliation>Department for Clinical and Experimental Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Barcelona, Spain</mods:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department for Clinical and Experimental Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Barcelona</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<mods:affiliation>Graduate School of Cellular and Molecular Neuroscience, International Max Planck Research School, Graduate Training Center of Neuroscience, Eberhard‐Karls University, Tübingen, Germany</mods:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Graduate School of Cellular and Molecular Neuroscience, International Max Planck Research School, Graduate Training Center of Neuroscience, Eberhard‐Karls University, Tübingen</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Waibel, Stefan" sort="Waibel, Stefan" uniqKey="Waibel S" first="Stefan" last="Waibel">Stefan Waibel</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, University of Ulm, Ulm, Germany</mods:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurology, University of Ulm, Ulm</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name>
<affiliation wicri:level="1">
<mods:affiliation>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck, Germany</mods:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Weber, Markus" sort="Weber, Markus" uniqKey="Weber M" first="Markus" last="Weber">Markus Weber</name>
<affiliation wicri:level="1">
<mods:affiliation>Neuromuscular Diseases Unit, Kantonspital St Gallen, St Gallen, Switzerland</mods:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Neuromuscular Diseases Unit, Kantonspital St Gallen, St Gallen</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Van Der Kooi, Anneke J" sort="Van Der Kooi, Anneke J" uniqKey="Van Der Kooi A" first="Anneke J." last="Van Der Kooi">Anneke J. Van Der Kooi</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, Amsterdam Medical Center, Amsterdam, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Amsterdam Medical Center, Amsterdam</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="De Visser, Marianne" sort="De Visser, Marianne" uniqKey="De Visser M" first="Marianne" last="De Visser">Marianne De Visser</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, Amsterdam Medical Center, Amsterdam, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Amsterdam Medical Center, Amsterdam</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Verbaan, Dagmar" sort="Verbaan, Dagmar" uniqKey="Verbaan D" first="Dagmar" last="Verbaan">Dagmar Verbaan</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Leiden University Medical Center, Leiden</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Van Hilten, Jacobus J" sort="Van Hilten, Jacobus J" uniqKey="Van Hilten J" first="Jacobus J." last="Van Hilten">Jacobus J. Van Hilten</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Leiden University Medical Center, Leiden</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Center, Amsterdam, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Center, Amsterdam</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hennekam, Eric A M" sort="Hennekam, Eric A M" uniqKey="Hennekam E" first="Eric A. M." last="Hennekam">Eric A. M. Hennekam</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Medical Genetics, University Medical Center Utrecht, Utrecht</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cuppen, Edwin" sort="Cuppen, Edwin" uniqKey="Cuppen E" first="Edwin" last="Cuppen">Edwin Cuppen</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Medical Genetics, University Medical Center Utrecht, Utrecht</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<mods:affiliation>Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Royal Netherlands Academy of Sciences, Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Royal Netherlands Academy of Sciences, Utrecht</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Berg, Daniela" sort="Berg, Daniela" uniqKey="Berg D" first="Daniela" last="Berg">Daniela Berg</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Brown Jr, Robert H" sort="Brown Jr, Robert H" uniqKey="Brown Jr R" first="Robert H." last="Brown Jr">Robert H. Brown Jr</name>
<affiliation wicri:level="2">
<mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Neurology, University of Massachusetts Medical School, Worcester</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Silani, Vincenzo" sort="Silani, Vincenzo" uniqKey="Silani V" first="Vincenzo" last="Silani">Vincenzo Silani</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy</mods:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, University of Milan Medical School, “Dino Ferrari” Center, Milan, Italy</mods:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Neurology, University of Milan Medical School, “Dino Ferrari” Center, Milan</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name>
<affiliation wicri:level="1">
<mods:affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Tübingen, Germany</mods:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Tübingen</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Ludolph, Albert C" sort="Ludolph, Albert C" uniqKey="Ludolph A" first="Albert C." last="Ludolph">Albert C. Ludolph</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, University of Ulm, Ulm, Germany</mods:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurology, University of Ulm, Ulm</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Robberecht, Wim" sort="Robberecht, Wim" uniqKey="Robberecht W" first="Wim" last="Robberecht">Wim Robberecht</name>
<affiliation wicri:level="1">
<mods:affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</mods:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Experimental Neurology, University of Leuven, Leuven</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<mods:affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</mods:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</mods:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Ophoff, Roel A" sort="Ophoff, Roel A" uniqKey="Ophoff R" first="Roel A." last="Ophoff">Roel A. Ophoff</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Medical Genetics, University Medical Center Utrecht, Utrecht</wicri:regionArea>
</affiliation>
<affiliation wicri:level="2">
<mods:affiliation>University of California at Los Angeles Center for Neurobehavioral Genetics, Los Angeles, CA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Californie</region>
</placeName>
<wicri:cityArea>University of California at Los Angeles Center for Neurobehavioral Genetics, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Veldink, Jan H" sort="Veldink, Jan H" uniqKey="Veldink J" first="Jan H." last="Veldink">Jan H. Veldink</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Pasterkamp, R Jeroen" sort="Pasterkamp, R Jeroen" uniqKey="Pasterkamp R" first="R. Jeroen" last="Pasterkamp">R. Jeroen Pasterkamp</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="De Bakker, Paul I W" sort="De Bakker, Paul I W" uniqKey="De Bakker P" first="Paul I. W." last="De Bakker">Paul I. W. De Bakker</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Medical Genetics, University Medical Center Utrecht, Utrecht</wicri:regionArea>
</affiliation>
<affiliation wicri:level="2">
<mods:affiliation>Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<mods:affiliation>Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge</wicri:cityArea>
</affiliation>
<affiliation wicri:level="1">
<mods:affiliation>Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Landers, John E" sort="Landers, John E" uniqKey="Landers J" first="John E." last="Landers">John E. Landers</name>
<affiliation wicri:level="2">
<mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Neurology, University of Massachusetts Medical School, Worcester</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Van De Warrenburg, Bart P" sort="Van De Warrenburg, Bart P" uniqKey="Van De Warrenburg B" first="Bart P." last="Van De Warrenburg">Bart P. Van De Warrenburg</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<mods:affiliation>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Van Den Berg, Leonard H" sort="Van Den Berg, Leonard H" uniqKey="Van Den Berg L" first="Leonard H." last="Van Den Berg">Leonard H. Van Den Berg</name>
<affiliation wicri:level="1">
<mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<mods:affiliation>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands</mods:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series>
<title level="j">Annals of Neurology</title>
<title level="j" type="abbrev">Ann Neurol.</title>
<idno type="ISSN">0364-5134</idno>
<idno type="eISSN">1531-8249</idno>
<imprint>
<publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher>
<pubPlace>Hoboken</pubPlace>
<date type="published" when="2011-12">2011-12</date>
<biblScope unit="volume">70</biblScope>
<biblScope unit="issue">6</biblScope>
<biblScope unit="page" from="964">964</biblScope>
<biblScope unit="page" to="973">973</biblScope>
</imprint>
<idno type="ISSN">0364-5134</idno>
</series>
<idno type="istex">1104402D2CD5B78610B101FB2326A7D93EC038A3</idno>
<idno type="DOI">10.1002/ana.22611</idno>
<idno type="ArticleID">ANA22611</idno>
</biblStruct>
</sourceDesc>
<seriesStmt>
<idno type="ISSN">0364-5134</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass></textClass>
<langUsage>
<language ident="en">en</language>
</langUsage>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Objective:: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. Methods:: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel‐Haenszel procedure was used to estimate odds ratios. Results:: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10−6 for ALS and p = 4.3 × 10−5 for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. Interpretation:: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD. ANN NEUROL 2011;70:964–973</div>
</front>
</TEI>
</record>

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