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Only one gain\u2010of\u2010function mutation in the highly conserved suppressor domain of\n                    <jats:italic>ITPR1<\/jats:italic>\n                    has been previously reported. We report a novel\n                    <jats:italic>de novo ITPR1<\/jats:italic>\n                    variant (p.(Tyr131His)) detected by whole genome sequencing in a child with an unexplained movement disorder, characterized by tremor and dystonia, concurrent with a second diagnosis of Myhre syndrome. The proband's movement disorder characteristics share much overlap with previously reported individuals with suppressor domain variants; however, she does not have ataxia. We provide functional evidence of this variant's gain\u2010of\u2010function consequence via in\u00a0vitro experiments of inositol 1,4,5\u2010triphosphate\u2010mediated calcium release. Our findings deepen the knowledge of\n                    <jats:italic>ITPR1<\/jats:italic>\n                    \u2010mediated movement disorders, expanding the phenotypic spectrum to include movement disorders without ataxia.\n                  <\/jats:p>","DOI":"10.1002\/ajmga.70069","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T14:45:27Z","timestamp":1770389127000},"page":"1261-1266","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Gain\u2010of\u2010Function\n                    <scp>\n                      <i>ITPR1<\/i>\n                    <\/scp>\n                    Variant Associated With a Movement Disorder Characterized by Tremor and Dystonia"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7466-7209","authenticated-orcid":false,"given":"Emilie T.","family":"Th\u00e9berge","sequence":"first","affiliation":[{"name":"Department of Medical Genetics University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7830-132X","authenticated-orcid":false,"given":"Bo","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Libin Cardiovascular Institute University of Calgary  Calgary Canada"},{"name":"Medical School Kunming University of Science and Technology  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiwu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Libin Cardiovascular Institute University of Calgary  Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arezoo","family":"Mohajeri","sequence":"additional","affiliation":[{"name":"British Columbia Children's &amp; Women's Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara D. M.","family":"Van Karnebeek","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Human Genetics, Emma Center for Personalized Medicine Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius F.","family":"Boerkoel","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of British Columbia  Vancouver British Columbia Canada"},{"name":"British Columbia Children's &amp; Women's Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Huynh","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of British Columbia  Vancouver British Columbia Canada"},{"name":"British Columbia Children's &amp; Women's Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2573-2489","authenticated-orcid":false,"given":"Gabriella","family":"Horvath","sequence":"additional","affiliation":[{"name":"British Columbia Children's &amp; Women's Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. R. Wayne","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Libin Cardiovascular Institute University of Calgary  Calgary Canada"},{"name":"Department of Physiology and Biophysics Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0636-123X","authenticated-orcid":false,"given":"Anna","family":"Lehman","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811129115"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-895X(24)23151-5"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-017-8545-5"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2011.03366.x"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.05.009"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9041096"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15840"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021119-034433"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000311277.71046.a0"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6439"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13991"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2013.00156"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-67"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.14884"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073816664836"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1993.1064"},{"key":"e_1_2_13_18_1","volume-title":"GeneReviews","author":"Lin A. 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