{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:03:26Z","timestamp":1784091806251,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Defects of mitochondrial ATP synthase (ATPase) represent an emerging, yet incompletely understood group of neurodevelopmental diseases with abnormal movements.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to redefine the phenotypic and mutational spectrum of movement disorders linked to the ATPase subunit\u2010encoding genes <jats:italic>ATP5F1A<\/jats:italic> and <jats:italic>ATP5F1B<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited regionally distant patients who had been genome or exome sequenced. Fibroblast cultures from two patients were established to perform RNA sequencing, immunoblotting, mass spectrometry\u2013based high\u2010throughput quantitative proteomics, and ATPase activity assays. In silico three\u2010dimensional missense variant modeling was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a patient with developmental delay, myoclonic dystonia, and spasticity who carried a heterozygous frameshift c.1404del (p.Glu469Serfs*3) variant in <jats:italic>ATP5F1A<\/jats:italic>. The patient's cells exhibited significant reductions in <jats:italic>ATP5F1A<\/jats:italic> mRNA, underexpression of the \u03b1\u2010subunit of ATPase in association with other aberrantly expressed ATPase components, and compromised ATPase activity. In addition, a novel deleterious heterozygous <jats:italic>ATP5F1A<\/jats:italic> missense c.1252G&gt;A (p.Gly418Arg) variant was discovered, shared by three patients from two families with hereditary spastic paraplegia (HSP). This variant mapped to a functionally important intersubunit communication site. A third heterozygous variant, c.1074+1G&gt;T, affected a canonical donor splice site of <jats:italic>ATP5F1B<\/jats:italic> and resulted in exon skipping with significantly diminished <jats:italic>ATP5F1B<\/jats:italic> mRNA levels, as well as impaired ATPase activity. The associated phenotype consisted of cerebral palsy (CP) with prominent generalized dystonia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data confirm and expand the role of dominant <jats:italic>ATP5F1A<\/jats:italic> and <jats:italic>ATP5F1B<\/jats:italic> variants in neurodevelopmental movement disorders. <jats:italic>ATP5F1A<\/jats:italic>\/<jats:italic>ATP5F1B<\/jats:italic>\u2010related ATPase diseases should be considered as a cause of dystonia, HSP, and CP. \u00a9 2025 The Author(s). <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.30209","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T05:51:00Z","timestamp":1745560260000},"page":"1388-1400","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Expanding the Allelic and Clinical Heterogeneity of Movement Disorders Linked to Defects of Mitochondrial Adenosine Triphosphate Synthase"],"prefix":"10.1002","volume":"40","author":[{"given":"Philip","family":"Harrer","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, School of Medicine and Health, Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6607-5983","authenticated-orcid":false,"given":"Magdalena","family":"Krygier","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurology Medical University of Gdansk  Gdansk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-3082","authenticated-orcid":false,"given":"Martin","family":"Krenn","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences &amp; Mental Health, Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Kittke","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine and Health, Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Danis","sequence":"additional","affiliation":[{"name":"Neurological Clinic of Faculty Hospital Trnava and Slovak Health University Bratislava  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgi","family":"Krastev","sequence":"additional","affiliation":[{"name":"Neurological Clinic of Faculty Hospital Trnava and Slovak Health University Bratislava  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Saparov","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine and Health, Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen  Munich Germany"},{"name":"Institute for Advanced Study, Technical University of Munich  Garching Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Pichon","sequence":"additional","affiliation":[{"name":"CRMR Neurogenetique, Service de Neurologie, Centre Hospitalier, Universitaire d\u2019Angers  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marl\u00e8ne","family":"Malbos","sequence":"additional","affiliation":[{"name":"CRMRs \u201cAnomalies du D\u00e9veloppement et syndromes malformatifs\u201d et \u201cD\u00e9ficiences Intellectuelles de causes rares,\u201d FHU\u2010TRANSLAD, CHU Dijon Bourgogne  Dijon France"},{"name":"Laboratoire de G\u00e9nomique M\u00e9dicale, UF Innovation en diagnostic g\u00e9nomique des maladies rares, CHU Dijon Bourgogne  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Scherer","sequence":"additional","affiliation":[{"name":"CRMR Neurogenetique, Service de Neurologie, Centre Hospitalier, Universitaire d\u2019Angers  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Dzinovic","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine and Health, Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5497-8715","authenticated-orcid":false,"given":"Matej","family":"Skorvanek","sequence":"additional","affiliation":[{"name":"Department of Neurology P.J. Safarik University  Kosice Slovakia"},{"name":"Department of Neurology University Hospital of L. Pasteur  Kosice Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Kopajtich","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine and Health, Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Prokisch","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine and Health, Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Silvaieh","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences &amp; Mental Health, Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Grisold","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences &amp; Mental Health, Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mazurkiewicz\u2010Be\u0142dzi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurology Medical University of Gdansk  Gdansk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Madeleine","family":"de Sainte Agathe","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Sorbonne Universit\u00e9, AP\u2010HP Sorbonne Universit\u00e9  Paris France"},{"name":"Laboratoire de Biologie M\u00e9dicale Multi\u2010Site SeqOIA, Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Winkelmann","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine and Health, Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen  Munich Germany"},{"name":"DZPG (German Center for Mental Health)  Munich Germany"},{"name":"Munich Cluster for Systems Neurology, SyNergy  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4626-9588","authenticated-orcid":false,"given":"Jan","family":"Necpal","sequence":"additional","affiliation":[{"name":"Department of Neurology Zvolen Hospital  Zvolen Slovakia"},{"name":"Parkinsonism and Movement Disorders Treatment Center, Zvolen Hospital  Zvolen Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9732-8947","authenticated-orcid":false,"given":"Robert","family":"Jech","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience First Faculty of Medicine Charles University and General University Hospital in Prague  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8112-9153","authenticated-orcid":false,"given":"Michael","family":"Zech","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine and Health, Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen  Munich Germany"},{"name":"Institute for Advanced Study, Technical University of Munich  Garching Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1343653"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9382-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00329"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki033"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-024-12447-5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26293"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29657"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad068"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00956-0"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2202949"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt086"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182918c40"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22844"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30312-4"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prdoa.2024.100267"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2022-108803"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15824"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2024.02.005"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaf059"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.136"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.016"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg7492"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.015"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab314"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.07.011"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.01.020"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy231"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.012047"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.06.012"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30235-2"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1222"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.30066"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02912-z"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01686-x"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.014"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-023-00909-9"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.12.013"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.30209","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:51:21Z","timestamp":1760953881000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.30209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,25]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/mds.30209"],"URL":"https:\/\/doi.org\/10.1002\/mds.30209","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,25]]},"assertion":[{"value":"2025-01-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}