Biallelic Mutations in PDE10A Lead to Loss of Striatal PDE10A and a Hyperkinetic Movement Disorder with Onset in Infancy.
Identifieur interne : 000312 ( PubMed/Checkpoint ); précédent : 000311; suivant : 000313Biallelic Mutations in PDE10A Lead to Loss of Striatal PDE10A and a Hyperkinetic Movement Disorder with Onset in Infancy.
Auteurs : Christine P. Diggle [Royaume-Uni] ; Stacey J. Sukoff Rizzo [États-Unis] ; Michael Popiolek [États-Unis] ; Reetta Hinttala [Finlande] ; Jan-Philip Schülke [États-Unis] ; Manju A. Kurian [Royaume-Uni] ; Ian M. Carr [Royaume-Uni] ; Alexander F. Markham [Royaume-Uni] ; David T. Bonthron [Royaume-Uni] ; Christopher Watson [Royaume-Uni] ; Saghira Malik Sharif [Royaume-Uni] ; Veronica Reinhart [États-Unis] ; Larry C. James [États-Unis] ; Michelle A. Vanase-Frawley [États-Unis] ; Erik Charych [États-Unis] ; Melanie Allen [États-Unis] ; John Harms [États-Unis] ; Christopher J. Schmidt [États-Unis] ; Joanne Ng [Royaume-Uni] ; Karen Pysden [Royaume-Uni] ; Christine Strick [États-Unis] ; P Ivi Vieira [Finlande] ; Katariina Mankinen [Finlande] ; Hannaleena Kokkonen [Finlande] ; Matti Kallioinen [Finlande] ; Raija Sormunen [Finlande] ; Juha O. Rinne [Finlande] ; Jarkko Johansson [Finlande] ; Kati Alakurtti [Finlande] ; Laura Huilaja [Finlande] ; Tiina Hurskainen [Finlande] ; Kaisa Tasanen [Finlande] ; Eija Anttila [Finlande] ; Tiago Reis Marques [Royaume-Uni] ; Oliver Howes [Royaume-Uni] ; Marius Politis [Royaume-Uni] ; Somayyeh Fahiminiya [Canada] ; Khanh Q. Nguyen [Canada] ; Jacek Majewski [Canada] ; Johanna Uusimaa [Finlande] ; Eamonn Sheridan [Royaume-Uni] ; Nicholas J. Brandon [États-Unis]Source :
- American journal of human genetics [ 1537-6605 ] ; 2016.
English descriptors
- KwdEn :
- Alleles, Amino Acid Sequence, Animals, Corpus Striatum (pathology), Disease Models, Animal, Gene Expression Regulation, Genetic Variation, HEK293 Cells, Humans, Hyperkinesis (diagnosis), Hyperkinesis (genetics), Hyperkinesis (pathology), Male, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Mutation, Pedigree, Phosphodiesterase Inhibitors (metabolism), Phosphoric Diester Hydrolases (genetics), Sequence Alignment.
- MESH :
- chemical , genetics : Phosphoric Diester Hydrolases.
- chemical , metabolism : Phosphodiesterase Inhibitors.
- diagnosis : Hyperkinesis.
- genetics : Hyperkinesis.
- pathology : Corpus Striatum, Hyperkinesis.
- Alleles, Amino Acid Sequence, Animals, Disease Models, Animal, Gene Expression Regulation, Genetic Variation, HEK293 Cells, Humans, Male, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Mutation, Pedigree, Sequence Alignment.
Abstract
Deficits in the basal ganglia pathways modulating cortical motor activity underlie both Parkinson disease (PD) and Huntington disease (HD). Phosphodiesterase 10A (PDE10A) is enriched in the striatum, and animal data suggest that it is a key regulator of this circuitry. Here, we report on germline PDE10A mutations in eight individuals from two families affected by a hyperkinetic movement disorder due to homozygous mutations c.320A>G (p.Tyr107Cys) and c.346G>C (p.Ala116Pro). Both mutations lead to a reduction in PDE10A levels in recombinant cellular systems, and critically, positron-emission-tomography (PET) studies with a specific PDE10A ligand confirmed that the p.Tyr107Cys variant also reduced striatal PDE10A levels in one of the affected individuals. A knock-in mouse model carrying the homologous p.Tyr97Cys variant had decreased striatal PDE10A and also displayed motor abnormalities. Striatal preparations from this animal had an impaired capacity to degrade cyclic adenosine monophosphate (cAMP) and a blunted pharmacological response to PDE10A inhibitors. These observations highlight the critical role of PDE10A in motor control across species.
DOI: 10.1016/j.ajhg.2016.03.015
PubMed: 27058446
Affiliations:
- Canada, Finlande, Royaume-Uni, États-Unis
- Angleterre, Connecticut, Finlande occidentale, Grand Londres, Massachusetts, Québec, Yorkshire-et-Humber
- Leeds, Londres, Montréal, Turku
- University College de Londres, Université McGill, Université de Leeds
Links toward previous steps (curation, corpus...)
Links to Exploration step
pubmed:27058446Le document en format XML
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James</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Vanase Frawley, Michelle A" sort="Vanase Frawley, Michelle A" uniqKey="Vanase Frawley M" first="Michelle A" last="Vanase-Frawley">Michelle A. Vanase-Frawley</name><affiliation wicri:level="2"><nlm:affiliation>Pfizer Research and Development, Groton, CT 06340, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Pfizer Research and Development, Groton, CT 06340</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Charych, Erik" sort="Charych, Erik" uniqKey="Charych E" first="Erik" last="Charych">Erik Charych</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Allen, Melanie" sort="Allen, Melanie" uniqKey="Allen M" first="Melanie" last="Allen">Melanie Allen</name><affiliation wicri:level="2"><nlm:affiliation>Pfizer Research and Development, Groton, CT 06340, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Pfizer Research and Development, Groton, CT 06340</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Harms, John" sort="Harms, John" uniqKey="Harms J" first="John" last="Harms">John Harms</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Schmidt, Christopher J" sort="Schmidt, Christopher J" uniqKey="Schmidt C" first="Christopher J" last="Schmidt">Christopher J. Schmidt</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Ng, Joanne" sort="Ng, Joanne" uniqKey="Ng J" first="Joanne" last="Ng">Joanne Ng</name><affiliation wicri:level="4"><nlm:affiliation>Developmental Neurosciences Programme, UCL Institute of Child Health, London WC1N 1EH, UK; Institute of Women's Health, University College London, London WC1N 1EH, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Developmental Neurosciences Programme, UCL Institute of Child Health, London WC1N 1EH, UK; Institute of Women's Health, University College London, London WC1N 1EH</wicri:regionArea><orgName type="university">University College de Londres</orgName><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Pysden, Karen" sort="Pysden, Karen" uniqKey="Pysden K" first="Karen" last="Pysden">Karen Pysden</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Neurology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Pediatric Neurology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX</wicri:regionArea><wicri:noRegion>Leeds LS1 3EX</wicri:noRegion></affiliation></author><author><name sortKey="Strick, Christine" sort="Strick, Christine" uniqKey="Strick C" first="Christine" last="Strick">Christine Strick</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Vieira, P Ivi" sort="Vieira, P Ivi" uniqKey="Vieira P" first="P Ivi" last="Vieira">P Ivi Vieira</name><affiliation wicri:level="1"><nlm:affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu</wicri:regionArea><wicri:noRegion>90029 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Mankinen, Katariina" sort="Mankinen, Katariina" uniqKey="Mankinen K" first="Katariina" last="Mankinen">Katariina Mankinen</name><affiliation wicri:level="1"><nlm:affiliation>Länsi-Pohja Central Hospital, 94100 Kemi, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Länsi-Pohja Central Hospital, 94100 Kemi</wicri:regionArea><wicri:noRegion>94100 Kemi</wicri:noRegion></affiliation></author><author><name sortKey="Kokkonen, Hannaleena" sort="Kokkonen, Hannaleena" uniqKey="Kokkonen H" first="Hannaleena" last="Kokkonen">Hannaleena Kokkonen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Chemistry, University of Oulu, PO Box 5000, 90014, Oulu Finland; Northern Finland Laboratory Centre, Oulu University Hospital, PO Box 500, 90029 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Clinical Chemistry, University of Oulu, PO Box 5000, 90014, Oulu Finland; Northern Finland Laboratory Centre, Oulu University Hospital, PO Box 500, 90029 Oulu</wicri:regionArea><wicri:noRegion>90029 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Kallioinen, Matti" sort="Kallioinen, Matti" uniqKey="Kallioinen M" first="Matti" last="Kallioinen">Matti Kallioinen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Pathology, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu</wicri:regionArea><wicri:noRegion>90014 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Sormunen, Raija" sort="Sormunen, Raija" uniqKey="Sormunen R" first="Raija" last="Sormunen">Raija Sormunen</name><affiliation wicri:level="1"><nlm:affiliation>Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu, Finland; Department of Pathology, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu, Finland; Department of Pathology, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu</wicri:regionArea><wicri:noRegion>90014 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Rinne, Juha O" sort="Rinne, Juha O" uniqKey="Rinne J" first="Juha O" last="Rinne">Juha O. Rinne</name><affiliation wicri:level="1"><nlm:affiliation>Division of Clinical Neurosciences, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland; Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Division of Clinical Neurosciences, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland; Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Johansson, Jarkko" sort="Johansson, Jarkko" uniqKey="Johansson J" first="Jarkko" last="Johansson">Jarkko Johansson</name><affiliation wicri:level="1"><nlm:affiliation>Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Alakurtti, Kati" sort="Alakurtti, Kati" uniqKey="Alakurtti K" first="Kati" last="Alakurtti">Kati Alakurtti</name><affiliation wicri:level="1"><nlm:affiliation>Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland; Department of Diagnostic Radiology, University of Turku and Turku University Hospital, PO Box 52, 20521 Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland; Department of Diagnostic Radiology, University of Turku and Turku University Hospital, PO Box 52, 20521 Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Huilaja, Laura" sort="Huilaja, Laura" uniqKey="Huilaja L" first="Laura" last="Huilaja">Laura Huilaja</name><affiliation wicri:level="1"><nlm:affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu</wicri:regionArea><wicri:noRegion>90014 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Hurskainen, Tiina" sort="Hurskainen, Tiina" uniqKey="Hurskainen T" first="Tiina" last="Hurskainen">Tiina Hurskainen</name><affiliation wicri:level="1"><nlm:affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu</wicri:regionArea><wicri:noRegion>90014 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Tasanen, Kaisa" sort="Tasanen, Kaisa" uniqKey="Tasanen K" first="Kaisa" last="Tasanen">Kaisa Tasanen</name><affiliation wicri:level="1"><nlm:affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu</wicri:regionArea><wicri:noRegion>90014 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Anttila, Eija" sort="Anttila, Eija" uniqKey="Anttila E" first="Eija" last="Anttila">Eija Anttila</name><affiliation wicri:level="1"><nlm:affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu</wicri:regionArea><wicri:noRegion>90029 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Marques, Tiago Reis" sort="Marques, Tiago Reis" uniqKey="Marques T" first="Tiago Reis" last="Marques">Tiago Reis Marques</name><affiliation wicri:level="1"><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF</wicri:regionArea><wicri:noRegion>London SE5 8AF</wicri:noRegion></affiliation></author><author><name sortKey="Howes, Oliver" sort="Howes, Oliver" uniqKey="Howes O" first="Oliver" last="Howes">Oliver Howes</name><affiliation wicri:level="1"><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK; MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK; MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London W12 0NN</wicri:regionArea><wicri:noRegion>London W12 0NN</wicri:noRegion></affiliation></author><author><name sortKey="Politis, Marius" sort="Politis, Marius" uniqKey="Politis M" first="Marius" last="Politis">Marius Politis</name><affiliation wicri:level="1"><nlm:affiliation>Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF</wicri:regionArea><wicri:noRegion>London SE5 8AF</wicri:noRegion></affiliation></author><author><name sortKey="Fahiminiya, Somayyeh" sort="Fahiminiya, Somayyeh" uniqKey="Fahiminiya S" first="Somayyeh" last="Fahiminiya">Somayyeh Fahiminiya</name><affiliation wicri:level="4"><nlm:affiliation>Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University and Génome Québec Innovation Centre, Montreal, Quebec, QC H3A 0G1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University and Génome Québec Innovation Centre, Montreal, Quebec, QC H3A 0G1</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Nguyen, Khanh Q" sort="Nguyen, Khanh Q" uniqKey="Nguyen K" first="Khanh Q" last="Nguyen">Khanh Q. Nguyen</name><affiliation wicri:level="4"><nlm:affiliation>Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Majewski, Jacek" sort="Majewski, Jacek" uniqKey="Majewski J" first="Jacek" last="Majewski">Jacek Majewski</name><affiliation wicri:level="4"><nlm:affiliation>Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University and Génome Québec Innovation Centre, Montreal, Quebec, QC H3A 0G1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University and Génome Québec Innovation Centre, Montreal, Quebec, QC H3A 0G1</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Uusimaa, Johanna" sort="Uusimaa, Johanna" uniqKey="Uusimaa J" first="Johanna" last="Uusimaa">Johanna Uusimaa</name><affiliation wicri:level="1"><nlm:affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland; Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu, Finland. Electronic address: johanna.uusimaa@oulu.fi.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland; Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu</wicri:regionArea><wicri:noRegion>90014 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Sheridan, Eamonn" sort="Sheridan, Eamonn" uniqKey="Sheridan E" first="Eamonn" last="Sheridan">Eamonn Sheridan</name><affiliation wicri:level="4"><nlm:affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK. Electronic address: e.sheridan@leeds.ac.uk.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Medicine, University of Leeds, Leeds LS9 7TF</wicri:regionArea><orgName type="university">Université de Leeds</orgName><placeName><settlement type="city">Leeds</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Yorkshire-et-Humber</region></placeName></affiliation></author><author><name sortKey="Brandon, Nicholas J" sort="Brandon, Nicholas J" uniqKey="Brandon N" first="Nicholas J" last="Brandon">Nicholas J. Brandon</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA. Electronic address: nick.brandon@azneuro.com.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27058446</idno><idno type="pmid">27058446</idno><idno type="doi">10.1016/j.ajhg.2016.03.015</idno><idno type="wicri:Area/PubMed/Corpus">000250</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000250</idno><idno type="wicri:Area/PubMed/Curation">000250</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000250</idno><idno type="wicri:Area/PubMed/Checkpoint">000250</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000250</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Biallelic Mutations in PDE10A Lead to Loss of Striatal PDE10A and a Hyperkinetic Movement Disorder with Onset in Infancy.</title><author><name sortKey="Diggle, Christine P" sort="Diggle, Christine P" uniqKey="Diggle C" first="Christine P" last="Diggle">Christine P. Diggle</name><affiliation wicri:level="4"><nlm:affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Medicine, University of Leeds, Leeds LS9 7TF</wicri:regionArea><orgName type="university">Université de Leeds</orgName><placeName><settlement type="city">Leeds</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Yorkshire-et-Humber</region></placeName></affiliation></author><author><name sortKey="Sukoff Rizzo, Stacey J" sort="Sukoff Rizzo, Stacey J" uniqKey="Sukoff Rizzo S" first="Stacey J" last="Sukoff Rizzo">Stacey J. Sukoff Rizzo</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Popiolek, Michael" sort="Popiolek, Michael" uniqKey="Popiolek M" first="Michael" last="Popiolek">Michael Popiolek</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Hinttala, Reetta" sort="Hinttala, Reetta" uniqKey="Hinttala R" first="Reetta" last="Hinttala">Reetta Hinttala</name><affiliation wicri:level="1"><nlm:affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada; Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada; Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu</wicri:regionArea><wicri:noRegion>90014 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Schulke, Jan Philip" sort="Schulke, Jan Philip" uniqKey="Schulke J" first="Jan-Philip" last="Schülke">Jan-Philip Schülke</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Kurian, Manju A" sort="Kurian, Manju A" uniqKey="Kurian M" first="Manju A" last="Kurian">Manju A. Kurian</name><affiliation wicri:level="1"><nlm:affiliation>Developmental Neurosciences Programme, UCL Institute of Child Health, London WC1N 1EH, UK; Department of Neurology, Great Ormond Street Hospital, London WC1N 1EH, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Developmental Neurosciences Programme, UCL Institute of Child Health, London WC1N 1EH, UK; Department of Neurology, Great Ormond Street Hospital, London WC1N 1EH</wicri:regionArea><wicri:noRegion>London WC1N 1EH</wicri:noRegion></affiliation></author><author><name sortKey="Carr, Ian M" sort="Carr, Ian M" uniqKey="Carr I" first="Ian M" last="Carr">Ian M. Carr</name><affiliation wicri:level="4"><nlm:affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Medicine, University of Leeds, Leeds LS9 7TF</wicri:regionArea><orgName type="university">Université de Leeds</orgName><placeName><settlement type="city">Leeds</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Yorkshire-et-Humber</region></placeName></affiliation></author><author><name sortKey="Markham, Alexander F" sort="Markham, Alexander F" uniqKey="Markham A" first="Alexander F" last="Markham">Alexander F. Markham</name><affiliation wicri:level="4"><nlm:affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Medicine, University of Leeds, Leeds LS9 7TF</wicri:regionArea><orgName type="university">Université de Leeds</orgName><placeName><settlement type="city">Leeds</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Yorkshire-et-Humber</region></placeName></affiliation></author><author><name sortKey="Bonthron, David T" sort="Bonthron, David T" uniqKey="Bonthron D" first="David T" last="Bonthron">David T. Bonthron</name><affiliation wicri:level="4"><nlm:affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Medicine, University of Leeds, Leeds LS9 7TF</wicri:regionArea><orgName type="university">Université de Leeds</orgName><placeName><settlement type="city">Leeds</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Yorkshire-et-Humber</region></placeName></affiliation></author><author><name sortKey="Watson, Christopher" sort="Watson, Christopher" uniqKey="Watson C" first="Christopher" last="Watson">Christopher Watson</name><affiliation wicri:level="4"><nlm:affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Medicine, University of Leeds, Leeds LS9 7TF</wicri:regionArea><orgName type="university">Université de Leeds</orgName><placeName><settlement type="city">Leeds</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Yorkshire-et-Humber</region></placeName></affiliation></author><author><name sortKey="Sharif, Saghira Malik" sort="Sharif, Saghira Malik" uniqKey="Sharif S" first="Saghira Malik" last="Sharif">Saghira Malik Sharif</name><affiliation wicri:level="4"><nlm:affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Medicine, University of Leeds, Leeds LS9 7TF</wicri:regionArea><orgName type="university">Université de Leeds</orgName><placeName><settlement type="city">Leeds</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Yorkshire-et-Humber</region></placeName></affiliation></author><author><name sortKey="Reinhart, Veronica" sort="Reinhart, Veronica" uniqKey="Reinhart V" first="Veronica" last="Reinhart">Veronica Reinhart</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="James, Larry C" sort="James, Larry C" uniqKey="James L" first="Larry C" last="James">Larry C. James</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Vanase Frawley, Michelle A" sort="Vanase Frawley, Michelle A" uniqKey="Vanase Frawley M" first="Michelle A" last="Vanase-Frawley">Michelle A. Vanase-Frawley</name><affiliation wicri:level="2"><nlm:affiliation>Pfizer Research and Development, Groton, CT 06340, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Pfizer Research and Development, Groton, CT 06340</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Charych, Erik" sort="Charych, Erik" uniqKey="Charych E" first="Erik" last="Charych">Erik Charych</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Allen, Melanie" sort="Allen, Melanie" uniqKey="Allen M" first="Melanie" last="Allen">Melanie Allen</name><affiliation wicri:level="2"><nlm:affiliation>Pfizer Research and Development, Groton, CT 06340, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Pfizer Research and Development, Groton, CT 06340</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Harms, John" sort="Harms, John" uniqKey="Harms J" first="John" last="Harms">John Harms</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Schmidt, Christopher J" sort="Schmidt, Christopher J" uniqKey="Schmidt C" first="Christopher J" last="Schmidt">Christopher J. Schmidt</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Ng, Joanne" sort="Ng, Joanne" uniqKey="Ng J" first="Joanne" last="Ng">Joanne Ng</name><affiliation wicri:level="4"><nlm:affiliation>Developmental Neurosciences Programme, UCL Institute of Child Health, London WC1N 1EH, UK; Institute of Women's Health, University College London, London WC1N 1EH, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Developmental Neurosciences Programme, UCL Institute of Child Health, London WC1N 1EH, UK; Institute of Women's Health, University College London, London WC1N 1EH</wicri:regionArea><orgName type="university">University College de Londres</orgName><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Pysden, Karen" sort="Pysden, Karen" uniqKey="Pysden K" first="Karen" last="Pysden">Karen Pysden</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Neurology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Pediatric Neurology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX</wicri:regionArea><wicri:noRegion>Leeds LS1 3EX</wicri:noRegion></affiliation></author><author><name sortKey="Strick, Christine" sort="Strick, Christine" uniqKey="Strick C" first="Christine" last="Strick">Christine Strick</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Vieira, P Ivi" sort="Vieira, P Ivi" uniqKey="Vieira P" first="P Ivi" last="Vieira">P Ivi Vieira</name><affiliation wicri:level="1"><nlm:affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu</wicri:regionArea><wicri:noRegion>90029 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Mankinen, Katariina" sort="Mankinen, Katariina" uniqKey="Mankinen K" first="Katariina" last="Mankinen">Katariina Mankinen</name><affiliation wicri:level="1"><nlm:affiliation>Länsi-Pohja Central Hospital, 94100 Kemi, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Länsi-Pohja Central Hospital, 94100 Kemi</wicri:regionArea><wicri:noRegion>94100 Kemi</wicri:noRegion></affiliation></author><author><name sortKey="Kokkonen, Hannaleena" sort="Kokkonen, Hannaleena" uniqKey="Kokkonen H" first="Hannaleena" last="Kokkonen">Hannaleena Kokkonen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Chemistry, University of Oulu, PO Box 5000, 90014, Oulu Finland; Northern Finland Laboratory Centre, Oulu University Hospital, PO Box 500, 90029 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Clinical Chemistry, University of Oulu, PO Box 5000, 90014, Oulu Finland; Northern Finland Laboratory Centre, Oulu University Hospital, PO Box 500, 90029 Oulu</wicri:regionArea><wicri:noRegion>90029 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Kallioinen, Matti" sort="Kallioinen, Matti" uniqKey="Kallioinen M" first="Matti" last="Kallioinen">Matti Kallioinen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Pathology, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu</wicri:regionArea><wicri:noRegion>90014 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Sormunen, Raija" sort="Sormunen, Raija" uniqKey="Sormunen R" first="Raija" last="Sormunen">Raija Sormunen</name><affiliation wicri:level="1"><nlm:affiliation>Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu, Finland; Department of Pathology, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu, Finland; Department of Pathology, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu</wicri:regionArea><wicri:noRegion>90014 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Rinne, Juha O" sort="Rinne, Juha O" uniqKey="Rinne J" first="Juha O" last="Rinne">Juha O. Rinne</name><affiliation wicri:level="1"><nlm:affiliation>Division of Clinical Neurosciences, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland; Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Division of Clinical Neurosciences, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland; Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Johansson, Jarkko" sort="Johansson, Jarkko" uniqKey="Johansson J" first="Jarkko" last="Johansson">Jarkko Johansson</name><affiliation wicri:level="1"><nlm:affiliation>Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Alakurtti, Kati" sort="Alakurtti, Kati" uniqKey="Alakurtti K" first="Kati" last="Alakurtti">Kati Alakurtti</name><affiliation wicri:level="1"><nlm:affiliation>Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland; Department of Diagnostic Radiology, University of Turku and Turku University Hospital, PO Box 52, 20521 Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland; Department of Diagnostic Radiology, University of Turku and Turku University Hospital, PO Box 52, 20521 Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Huilaja, Laura" sort="Huilaja, Laura" uniqKey="Huilaja L" first="Laura" last="Huilaja">Laura Huilaja</name><affiliation wicri:level="1"><nlm:affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu</wicri:regionArea><wicri:noRegion>90014 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Hurskainen, Tiina" sort="Hurskainen, Tiina" uniqKey="Hurskainen T" first="Tiina" last="Hurskainen">Tiina Hurskainen</name><affiliation wicri:level="1"><nlm:affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu</wicri:regionArea><wicri:noRegion>90014 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Tasanen, Kaisa" sort="Tasanen, Kaisa" uniqKey="Tasanen K" first="Kaisa" last="Tasanen">Kaisa Tasanen</name><affiliation wicri:level="1"><nlm:affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu</wicri:regionArea><wicri:noRegion>90014 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Anttila, Eija" sort="Anttila, Eija" uniqKey="Anttila E" first="Eija" last="Anttila">Eija Anttila</name><affiliation wicri:level="1"><nlm:affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu</wicri:regionArea><wicri:noRegion>90029 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Marques, Tiago Reis" sort="Marques, Tiago Reis" uniqKey="Marques T" first="Tiago Reis" last="Marques">Tiago Reis Marques</name><affiliation wicri:level="1"><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF</wicri:regionArea><wicri:noRegion>London SE5 8AF</wicri:noRegion></affiliation></author><author><name sortKey="Howes, Oliver" sort="Howes, Oliver" uniqKey="Howes O" first="Oliver" last="Howes">Oliver Howes</name><affiliation wicri:level="1"><nlm:affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK; MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK; MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London W12 0NN</wicri:regionArea><wicri:noRegion>London W12 0NN</wicri:noRegion></affiliation></author><author><name sortKey="Politis, Marius" sort="Politis, Marius" uniqKey="Politis M" first="Marius" last="Politis">Marius Politis</name><affiliation wicri:level="1"><nlm:affiliation>Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF</wicri:regionArea><wicri:noRegion>London SE5 8AF</wicri:noRegion></affiliation></author><author><name sortKey="Fahiminiya, Somayyeh" sort="Fahiminiya, Somayyeh" uniqKey="Fahiminiya S" first="Somayyeh" last="Fahiminiya">Somayyeh Fahiminiya</name><affiliation wicri:level="4"><nlm:affiliation>Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University and Génome Québec Innovation Centre, Montreal, Quebec, QC H3A 0G1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University and Génome Québec Innovation Centre, Montreal, Quebec, QC H3A 0G1</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Nguyen, Khanh Q" sort="Nguyen, Khanh Q" uniqKey="Nguyen K" first="Khanh Q" last="Nguyen">Khanh Q. Nguyen</name><affiliation wicri:level="4"><nlm:affiliation>Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Majewski, Jacek" sort="Majewski, Jacek" uniqKey="Majewski J" first="Jacek" last="Majewski">Jacek Majewski</name><affiliation wicri:level="4"><nlm:affiliation>Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University and Génome Québec Innovation Centre, Montreal, Quebec, QC H3A 0G1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University and Génome Québec Innovation Centre, Montreal, Quebec, QC H3A 0G1</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Uusimaa, Johanna" sort="Uusimaa, Johanna" uniqKey="Uusimaa J" first="Johanna" last="Uusimaa">Johanna Uusimaa</name><affiliation wicri:level="1"><nlm:affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland; Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu, Finland. Electronic address: johanna.uusimaa@oulu.fi.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland; Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu</wicri:regionArea><wicri:noRegion>90014 Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Sheridan, Eamonn" sort="Sheridan, Eamonn" uniqKey="Sheridan E" first="Eamonn" last="Sheridan">Eamonn Sheridan</name><affiliation wicri:level="4"><nlm:affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK. Electronic address: e.sheridan@leeds.ac.uk.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Medicine, University of Leeds, Leeds LS9 7TF</wicri:regionArea><orgName type="university">Université de Leeds</orgName><placeName><settlement type="city">Leeds</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Yorkshire-et-Humber</region></placeName></affiliation></author><author><name sortKey="Brandon, Nicholas J" sort="Brandon, Nicholas J" uniqKey="Brandon N" first="Nicholas J" last="Brandon">Nicholas J. Brandon</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA. Electronic address: nick.brandon@azneuro.com.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author></analytic><series><title level="j">American journal of human genetics</title><idno type="eISSN">1537-6605</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alleles</term><term>Amino Acid Sequence</term><term>Animals</term><term>Corpus Striatum (pathology)</term><term>Disease Models, Animal</term><term>Gene Expression Regulation</term><term>Genetic Variation</term><term>HEK293 Cells</term><term>Humans</term><term>Hyperkinesis (diagnosis)</term><term>Hyperkinesis (genetics)</term><term>Hyperkinesis (pathology)</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Molecular Sequence Data</term><term>Mutation</term><term>Pedigree</term><term>Phosphodiesterase Inhibitors (metabolism)</term><term>Phosphoric Diester Hydrolases (genetics)</term><term>Sequence Alignment</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Phosphoric Diester Hydrolases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Phosphodiesterase Inhibitors</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Hyperkinesis</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Hyperkinesis</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Corpus Striatum</term><term>Hyperkinesis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Alleles</term><term>Amino Acid Sequence</term><term>Animals</term><term>Disease Models, Animal</term><term>Gene Expression Regulation</term><term>Genetic Variation</term><term>HEK293 Cells</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Molecular Sequence Data</term><term>Mutation</term><term>Pedigree</term><term>Sequence Alignment</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Deficits in the basal ganglia pathways modulating cortical motor activity underlie both Parkinson disease (PD) and Huntington disease (HD). Phosphodiesterase 10A (PDE10A) is enriched in the striatum, and animal data suggest that it is a key regulator of this circuitry. Here, we report on germline PDE10A mutations in eight individuals from two families affected by a hyperkinetic movement disorder due to homozygous mutations c.320A>G (p.Tyr107Cys) and c.346G>C (p.Ala116Pro). Both mutations lead to a reduction in PDE10A levels in recombinant cellular systems, and critically, positron-emission-tomography (PET) studies with a specific PDE10A ligand confirmed that the p.Tyr107Cys variant also reduced striatal PDE10A levels in one of the affected individuals. A knock-in mouse model carrying the homologous p.Tyr97Cys variant had decreased striatal PDE10A and also displayed motor abnormalities. Striatal preparations from this animal had an impaired capacity to degrade cyclic adenosine monophosphate (cAMP) and a blunted pharmacological response to PDE10A inhibitors. These observations highlight the critical role of PDE10A in motor control across species.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27058446</PMID><DateCreated><Year>2016</Year><Month>04</Month><Day>09</Day></DateCreated><DateCompleted><Year>2016</Year><Month>08</Month><Day>29</Day></DateCompleted><DateRevised><Year>2017</Year><Month>03</Month><Day>24</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1537-6605</ISSN><JournalIssue CitedMedium="Internet"><Volume>98</Volume><Issue>4</Issue><PubDate><Year>2016</Year><Month>Apr</Month><Day>07</Day></PubDate></JournalIssue><Title>American journal of human genetics</Title><ISOAbbreviation>Am. J. Hum. Genet.</ISOAbbreviation></Journal><ArticleTitle>Biallelic Mutations in PDE10A Lead to Loss of Striatal PDE10A and a Hyperkinetic Movement Disorder with Onset in Infancy.</ArticleTitle><Pagination><MedlinePgn>735-43</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ajhg.2016.03.015</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0002-9297(16)30050-7</ELocationID><Abstract><AbstractText>Deficits in the basal ganglia pathways modulating cortical motor activity underlie both Parkinson disease (PD) and Huntington disease (HD). Phosphodiesterase 10A (PDE10A) is enriched in the striatum, and animal data suggest that it is a key regulator of this circuitry. Here, we report on germline PDE10A mutations in eight individuals from two families affected by a hyperkinetic movement disorder due to homozygous mutations c.320A>G (p.Tyr107Cys) and c.346G>C (p.Ala116Pro). Both mutations lead to a reduction in PDE10A levels in recombinant cellular systems, and critically, positron-emission-tomography (PET) studies with a specific PDE10A ligand confirmed that the p.Tyr107Cys variant also reduced striatal PDE10A levels in one of the affected individuals. A knock-in mouse model carrying the homologous p.Tyr97Cys variant had decreased striatal PDE10A and also displayed motor abnormalities. Striatal preparations from this animal had an impaired capacity to degrade cyclic adenosine monophosphate (cAMP) and a blunted pharmacological response to PDE10A inhibitors. These observations highlight the critical role of PDE10A in motor control across species.</AbstractText><CopyrightInformation>Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Diggle</LastName><ForeName>Christine P</ForeName><Initials>CP</Initials><AffiliationInfo><Affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sukoff Rizzo</LastName><ForeName>Stacey J</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Popiolek</LastName><ForeName>Michael</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hinttala</LastName><ForeName>Reetta</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada; Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schülke</LastName><ForeName>Jan-Philip</ForeName><Initials>JP</Initials><AffiliationInfo><Affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kurian</LastName><ForeName>Manju A</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>Developmental Neurosciences Programme, UCL Institute of Child Health, London WC1N 1EH, UK; Department of Neurology, Great Ormond Street Hospital, London WC1N 1EH, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carr</LastName><ForeName>Ian M</ForeName><Initials>IM</Initials><AffiliationInfo><Affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Markham</LastName><ForeName>Alexander F</ForeName><Initials>AF</Initials><AffiliationInfo><Affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bonthron</LastName><ForeName>David T</ForeName><Initials>DT</Initials><AffiliationInfo><Affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Watson</LastName><ForeName>Christopher</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sharif</LastName><ForeName>Saghira Malik</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Reinhart</LastName><ForeName>Veronica</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>James</LastName><ForeName>Larry C</ForeName><Initials>LC</Initials><AffiliationInfo><Affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vanase-Frawley</LastName><ForeName>Michelle A</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>Pfizer Research and Development, Groton, CT 06340, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Charych</LastName><ForeName>Erik</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Allen</LastName><ForeName>Melanie</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Pfizer Research and Development, Groton, CT 06340, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Harms</LastName><ForeName>John</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schmidt</LastName><ForeName>Christopher J</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ng</LastName><ForeName>Joanne</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Developmental Neurosciences Programme, UCL Institute of Child Health, London WC1N 1EH, UK; Institute of Women's Health, University College London, London WC1N 1EH, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pysden</LastName><ForeName>Karen</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Pediatric Neurology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Strick</LastName><ForeName>Christine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vieira</LastName><ForeName>Päivi</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mankinen</LastName><ForeName>Katariina</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Länsi-Pohja Central Hospital, 94100 Kemi, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kokkonen</LastName><ForeName>Hannaleena</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Clinical Chemistry, University of Oulu, PO Box 5000, 90014, Oulu Finland; Northern Finland Laboratory Centre, Oulu University Hospital, PO Box 500, 90029 Oulu, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kallioinen</LastName><ForeName>Matti</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Pathology, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sormunen</LastName><ForeName>Raija</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu, Finland; Department of Pathology, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rinne</LastName><ForeName>Juha O</ForeName><Initials>JO</Initials><AffiliationInfo><Affiliation>Division of Clinical Neurosciences, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland; Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johansson</LastName><ForeName>Jarkko</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Alakurtti</LastName><ForeName>Kati</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Turku PET Centre, Turku University Hospital and University of Turku, PO Box 52, 20521 Turku, Finland; Department of Diagnostic Radiology, University of Turku and Turku University Hospital, PO Box 52, 20521 Turku, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huilaja</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hurskainen</LastName><ForeName>Tiina</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tasanen</LastName><ForeName>Kaisa</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Dermatology and Oulu Center for Cell-Matrix Research, Oulu University Hospital and University of Oulu, PO Box 5000, 90014 Oulu, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Anttila</LastName><ForeName>Eija</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marques</LastName><ForeName>Tiago Reis</ForeName><Initials>TR</Initials><AffiliationInfo><Affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Howes</LastName><ForeName>Oliver</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK; MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Politis</LastName><ForeName>Marius</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fahiminiya</LastName><ForeName>Somayyeh</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University and Génome Québec Innovation Centre, Montreal, Quebec, QC H3A 0G1, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nguyen</LastName><ForeName>Khanh Q</ForeName><Initials>KQ</Initials><AffiliationInfo><Affiliation>Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Majewski</LastName><ForeName>Jacek</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University and Génome Québec Innovation Centre, Montreal, Quebec, QC H3A 0G1, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Uusimaa</LastName><ForeName>Johanna</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, PO Box 23, 90029 Oulu, Finland; Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu, Finland. Electronic address: johanna.uusimaa@oulu.fi.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sheridan</LastName><ForeName>Eamonn</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>School of Medicine, University of Leeds, Leeds LS9 7TF, UK. Electronic address: e.sheridan@leeds.ac.uk.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brandon</LastName><ForeName>Nicholas J</ForeName><Initials>NJ</Initials><AffiliationInfo><Affiliation>Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA 02139, USA. 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UI="C119843">PDE10A protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.1.4.-</RegistryNumber><NameOfSubstance UI="C492284">Pde10a protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.1.4.-</RegistryNumber><NameOfSubstance UI="D010727">Phosphoric Diester Hydrolases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Hum Mutat. 2009 Jun;30(6):960-7</RefSource><PMID Version="1">19405095</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Ann Neurol. 2014 Apr;75(4):542-9</RefSource><PMID Version="1">24700542</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Exp Cell Res. 1995 Dec;221(2):520-5</RefSource><PMID Version="1">7493652</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Adv Neurol. 2001;86:55-72</RefSource><PMID 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MajorTopicYN="N">Sequence Alignment</DescriptorName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC4833436 [Available on 10/07/16]</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>01</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>03</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>4</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>4</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>8</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27058446</ArticleId><ArticleId IdType="pii">S0002-9297(16)30050-7</ArticleId><ArticleId IdType="doi">10.1016/j.ajhg.2016.03.015</ArticleId><ArticleId IdType="pmc">PMC4833436</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li><li>Finlande</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Connecticut</li><li>Finlande occidentale</li><li>Grand Londres</li><li>Massachusetts</li><li>Québec</li><li>Yorkshire-et-Humber</li></region><settlement><li>Leeds</li><li>Londres</li><li>Montréal</li><li>Turku</li></settlement><orgName><li>University College de Londres</li><li>Université McGill</li><li>Université de Leeds</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Diggle, Christine P" sort="Diggle, Christine P" uniqKey="Diggle C" first="Christine P" last="Diggle">Christine P. Diggle</name></region><name sortKey="Bonthron, David T" sort="Bonthron, David T" uniqKey="Bonthron D" first="David T" last="Bonthron">David T. Bonthron</name><name sortKey="Carr, Ian M" sort="Carr, Ian M" uniqKey="Carr I" first="Ian M" last="Carr">Ian M. Carr</name><name sortKey="Howes, Oliver" sort="Howes, Oliver" uniqKey="Howes O" first="Oliver" last="Howes">Oliver Howes</name><name sortKey="Kurian, Manju A" sort="Kurian, Manju A" uniqKey="Kurian M" first="Manju A" last="Kurian">Manju A. Kurian</name><name sortKey="Markham, Alexander F" sort="Markham, Alexander F" uniqKey="Markham A" first="Alexander F" last="Markham">Alexander F. Markham</name><name sortKey="Marques, Tiago Reis" sort="Marques, Tiago Reis" uniqKey="Marques T" first="Tiago Reis" last="Marques">Tiago Reis Marques</name><name sortKey="Ng, Joanne" sort="Ng, Joanne" uniqKey="Ng J" first="Joanne" last="Ng">Joanne Ng</name><name sortKey="Politis, Marius" sort="Politis, Marius" uniqKey="Politis M" first="Marius" last="Politis">Marius Politis</name><name sortKey="Pysden, Karen" sort="Pysden, Karen" uniqKey="Pysden K" first="Karen" last="Pysden">Karen Pysden</name><name sortKey="Sharif, Saghira Malik" sort="Sharif, Saghira Malik" uniqKey="Sharif S" first="Saghira Malik" last="Sharif">Saghira Malik Sharif</name><name sortKey="Sheridan, Eamonn" sort="Sheridan, Eamonn" uniqKey="Sheridan E" first="Eamonn" last="Sheridan">Eamonn Sheridan</name><name sortKey="Watson, Christopher" sort="Watson, Christopher" uniqKey="Watson C" first="Christopher" last="Watson">Christopher Watson</name></country><country name="États-Unis"><region name="Massachusetts"><name sortKey="Sukoff Rizzo, Stacey J" sort="Sukoff Rizzo, Stacey J" uniqKey="Sukoff Rizzo S" first="Stacey J" last="Sukoff Rizzo">Stacey J. Sukoff Rizzo</name></region><name sortKey="Allen, Melanie" sort="Allen, Melanie" uniqKey="Allen M" first="Melanie" last="Allen">Melanie Allen</name><name sortKey="Brandon, Nicholas J" sort="Brandon, Nicholas J" uniqKey="Brandon N" first="Nicholas J" last="Brandon">Nicholas J. Brandon</name><name sortKey="Charych, Erik" sort="Charych, Erik" uniqKey="Charych E" first="Erik" last="Charych">Erik Charych</name><name sortKey="Harms, John" sort="Harms, John" uniqKey="Harms J" first="John" last="Harms">John Harms</name><name sortKey="James, Larry C" sort="James, Larry C" uniqKey="James L" first="Larry C" last="James">Larry C. James</name><name sortKey="Popiolek, Michael" sort="Popiolek, Michael" uniqKey="Popiolek M" first="Michael" last="Popiolek">Michael Popiolek</name><name sortKey="Reinhart, Veronica" sort="Reinhart, Veronica" uniqKey="Reinhart V" first="Veronica" last="Reinhart">Veronica Reinhart</name><name sortKey="Schmidt, Christopher J" sort="Schmidt, Christopher J" uniqKey="Schmidt C" first="Christopher J" last="Schmidt">Christopher J. Schmidt</name><name sortKey="Schulke, Jan Philip" sort="Schulke, Jan Philip" uniqKey="Schulke J" first="Jan-Philip" last="Schülke">Jan-Philip Schülke</name><name sortKey="Strick, Christine" sort="Strick, Christine" uniqKey="Strick C" first="Christine" last="Strick">Christine Strick</name><name sortKey="Vanase Frawley, Michelle A" sort="Vanase Frawley, Michelle A" uniqKey="Vanase Frawley M" first="Michelle A" last="Vanase-Frawley">Michelle A. Vanase-Frawley</name></country><country name="Finlande"><noRegion><name sortKey="Hinttala, Reetta" sort="Hinttala, Reetta" uniqKey="Hinttala R" first="Reetta" last="Hinttala">Reetta Hinttala</name></noRegion><name sortKey="Alakurtti, Kati" sort="Alakurtti, Kati" uniqKey="Alakurtti K" first="Kati" last="Alakurtti">Kati Alakurtti</name><name sortKey="Anttila, Eija" sort="Anttila, Eija" uniqKey="Anttila E" first="Eija" last="Anttila">Eija Anttila</name><name sortKey="Huilaja, Laura" sort="Huilaja, Laura" uniqKey="Huilaja L" first="Laura" last="Huilaja">Laura Huilaja</name><name sortKey="Hurskainen, Tiina" sort="Hurskainen, Tiina" uniqKey="Hurskainen T" first="Tiina" last="Hurskainen">Tiina Hurskainen</name><name sortKey="Johansson, Jarkko" sort="Johansson, Jarkko" uniqKey="Johansson J" first="Jarkko" last="Johansson">Jarkko Johansson</name><name sortKey="Kallioinen, Matti" sort="Kallioinen, Matti" uniqKey="Kallioinen M" first="Matti" last="Kallioinen">Matti Kallioinen</name><name sortKey="Kokkonen, Hannaleena" sort="Kokkonen, Hannaleena" uniqKey="Kokkonen H" first="Hannaleena" last="Kokkonen">Hannaleena Kokkonen</name><name sortKey="Mankinen, Katariina" sort="Mankinen, Katariina" uniqKey="Mankinen K" first="Katariina" last="Mankinen">Katariina Mankinen</name><name sortKey="Rinne, Juha O" sort="Rinne, Juha O" uniqKey="Rinne J" first="Juha O" last="Rinne">Juha O. Rinne</name><name sortKey="Sormunen, Raija" sort="Sormunen, Raija" uniqKey="Sormunen R" first="Raija" last="Sormunen">Raija Sormunen</name><name sortKey="Tasanen, Kaisa" sort="Tasanen, Kaisa" uniqKey="Tasanen K" first="Kaisa" last="Tasanen">Kaisa Tasanen</name><name sortKey="Uusimaa, Johanna" sort="Uusimaa, Johanna" uniqKey="Uusimaa J" first="Johanna" last="Uusimaa">Johanna Uusimaa</name><name sortKey="Vieira, P Ivi" sort="Vieira, P Ivi" uniqKey="Vieira P" first="P Ivi" last="Vieira">P Ivi Vieira</name></country><country name="Canada"><region name="Québec"><name sortKey="Fahiminiya, Somayyeh" sort="Fahiminiya, Somayyeh" uniqKey="Fahiminiya S" first="Somayyeh" last="Fahiminiya">Somayyeh Fahiminiya</name></region><name sortKey="Majewski, Jacek" sort="Majewski, Jacek" uniqKey="Majewski J" first="Jacek" last="Majewski">Jacek Majewski</name><name sortKey="Nguyen, Khanh Q" sort="Nguyen, Khanh Q" uniqKey="Nguyen K" first="Khanh Q" last="Nguyen">Khanh Q. 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