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A method of case\u2013control analysis was applied to identify the candidate genes. Whole\u2010cell patch\u2010clamp recording was applied to verify the electrophysiological impact of the identified variants. A mouse model with cerebellar heterozygous knockout of the candidate gene was developed via adeno\u2010associated virus injection, and dystonia\u2010like phenotype inducement and rotarod tests were performed. In vivo multiunit electrical recording was applied to investigate the change in neural excitability in knockout mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Heterozygous variants of potassium inwardly rectifying channel subfamily J member 10 (<jats:italic>KCNJ10<\/jats:italic>) clustered in PKD patients were compared with those in the control groups. Fifteen variants were detected in 16 of 522 probands (frequency\u2009=\u20093.07%). Patients with <jats:italic>KCNJ10<\/jats:italic> variants tended to have a milder manifestation compared to those with <jats:italic>PRRT2<\/jats:italic> (proline\u2010rich transmembrane protein 2) variants. <jats:italic>KCNJ10<\/jats:italic> variants partially altered the transmembrane location of inwardly rectifying potassium channel 4.1 (Kir4.1). The <jats:italic>Kcnj10<\/jats:italic> expression is consistent with the natural course of PKD. Variants resulted in different degrees of reduction in cell Kir4.1 currents, and mice with heterozygous conditional knockout of <jats:italic>Kcnj10<\/jats:italic> in the cerebellum presented dystonic posture, together with poor motor coordination and motor learning ability in rotarod tests. The firing rate of deep cerebellar nuclei was significantly elevated in <jats:italic>Kcnj10<\/jats:italic>\u2010cKO mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identified heterozygous variants of <jats:italic>KCNJ10<\/jats:italic> in PKD. Impaired function of Kir4.1 might lead to abnormal neuronal excitability, which attributed to PKD. \u00a9 2024 International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.30025","type":"journal-article","created":{"date-parts":[[2024,10,5]],"date-time":"2024-10-05T04:53:41Z","timestamp":1728104021000},"page":"2199-2210","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Heterozygous <scp><i>KCNJ10<\/i><\/scp> Variants Affecting Kir4.1 Channel Cause Paroxysmal Kinesigenic Dyskinesia"],"prefix":"10.1002","volume":"39","author":[{"given":"Xiaojun","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neurology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Neurological Rare Disease Biobank and Precision Diagnostic Technical Service Platform  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Fu","sequence":"additional","affiliation":[{"name":"Center for Brain Science, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingying","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Neurological Rare Disease Biobank and Precision Diagnostic Technical Service Platform  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Neurological Rare Disease Biobank and Precision Diagnostic Technical Service Platform  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Anatomy and Physiology Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Neurological Rare Disease Biobank and Precision Diagnostic Technical Service Platform  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Neurology Minhang Hospital, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences &amp; 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