{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T05:04:44Z","timestamp":1737522284847,"version":"3.33.0"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["112\u20102314\u2010B\u2010075\u2010034\u2010MY3","113\u20102634\u2010F\u2010039\u2010001"],"award-info":[{"award-number":["112\u20102314\u2010B\u2010075\u2010034\u2010MY3","113\u20102634\u2010F\u2010039\u2010001"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The genetic causes of a significant number of patients with cerebellar ataxia remain unsolved. Variations in the <jats:italic>ITM2B<\/jats:italic> gene, typically linked to dominantly inherited dementia, can sometimes present with cerebellar ataxia as an early symptom. This study aims to investigate the role of <jats:italic>ITM2B<\/jats:italic> variations in a Taiwanese cohort with unsolved cerebellar ataxia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genetic analysis of <jats:italic>ITM2B<\/jats:italic> was performed in 212 unrelated Taiwanese patients with unsolved cerebellar ataxia. Eight short tandem repeat markers flanking <jats:italic>ITM2B<\/jats:italic> were genotyped to analyze the associated haplotype. Affected carriers underwent comprehensive clinical evaluations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A heterozygous <jats:italic>ITM2B<\/jats:italic> variant, c.800G&gt;T (p.(Ter267LeuextTer11)), was identified in three patients. Haplotype analysis demonstrated a shared haplotype linked to this variant in the three families, suggesting a founder effect. The three probands and additional three affected relatives presented with cerebellar ataxia and unsteady gait with an average onset age of 43.2\u2009years. Most participants had no cognitive impairment at symptom onset but experienced memory decline, oculomotor disturbances, lower limb spasticity, and extensor plantar responses within 2\u20135\u2009years. Magnetic resonance imaging and spectroscopy revealed progressive extension of white matter hyperintensity over periventricular and subcortical regions, subtle hippocampal atrophy, preserved cerebellar volumes, and decreased N\u2010acetylaspartate\/creatine ratio over the vermis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p><jats:italic>ITM2B<\/jats:italic> mutations accounted for 1.4% of cerebellar ataxia cases in the Taiwanese cohort, with patients carrying <jats:italic>ITM2B<\/jats:italic> c.800G&gt;T descending from a common ancestor. This study underscores the importance of considering <jats:italic>ITM2B<\/jats:italic> variations as a potential cause of cerebellar ataxia, even in the absence of dementia at the initial presentation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52265","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T18:24:05Z","timestamp":1733250245000},"page":"158-168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating <i>ITM2B<\/i>\u2010associated ataxia in a Taiwanese cerebellar ataxia cohort"],"prefix":"10.1002","volume":"12","author":[{"given":"Shih\u2010Yu","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei Taiwan, ROC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Tsung","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei Taiwan, ROC"},{"name":"Department of Neurology National Yang Ming Chiao Tung University of Medicine  Taipei Taiwan, ROC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang\u2010Yang","family":"Jih","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei Taiwan, ROC"},{"name":"Department of Neurology National Yang Ming Chiao Tung University of Medicine  Taipei Taiwan, ROC"},{"name":"Department and Institute of Physiology, College of Medicine National Yang Ming Chiao Tung University  Taipei Taiwan, ROC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Sheun","family":"Tsai","sequence":"additional","affiliation":[{"name":"Cancer and Immunology Research Center National Yang Ming Chiao Tung University  Taipei Taiwan, ROC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuan\u2010Lin","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei Taiwan, ROC"},{"name":"Department of Neurology National Yang Ming Chiao Tung University of Medicine  Taipei Taiwan, ROC"},{"name":"Brain Research Center National Yang Ming Chiao Tung University  Taipei Taiwan, ROC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Ta","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neurological Institute Taichung Veterans General Hospital  Taichung Taiwan, ROC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9644-2086","authenticated-orcid":false,"given":"Yi\u2010Chu","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei Taiwan, ROC"},{"name":"Department of Neurology National Yang Ming Chiao Tung University of Medicine  Taipei Taiwan, ROC"},{"name":"Brain Research Center National Yang Ming Chiao Tung University  Taipei Taiwan, ROC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-164X","authenticated-orcid":false,"given":"Yi\u2010Chung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei Taiwan, ROC"},{"name":"Department of Neurology National Yang Ming Chiao Tung University of Medicine  Taipei Taiwan, ROC"},{"name":"Brain Research Center National Yang Ming Chiao Tung University  Taipei Taiwan, ROC"},{"name":"Center for Intelligent Drug Systems and Smart Bio\u2010devices (IDS2B) National Yang Ming Chiao Tung University  Hsinchu Taiwan, ROC"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-018-9076-4"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.58.7.1105"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00722.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000358801"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0177296"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac135"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1970.tb02219.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/21637"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.080076097"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/61.3.254"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/13554794.2019.1590603"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210176"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C500231200"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-131364"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.015679"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-96571-6"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03932-5"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2023.115465"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41340-9"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101089"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0891-08.2008"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63993-4"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2007.01.050"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.5.975"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-230051"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000219042.60538.92"},{"issue":"10","key":"e_1_2_10_28_1","first-page":"676","article-title":"Factor structure and explanatory variables of the mini\u2010mental state examination (MMSE) for elderly persons in Taiwan","volume":"100","author":"Shyu YI","year":"2001","journal-title":"J Formos Med Assoc"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047925"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci7070083"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64189-2.00012-3"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30193-4"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12186"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25245"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-009-5290-4"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2016.01.032"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-016-0818-5"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/13854046.2016.1165805"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0074-3"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-022-00382-6"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-020-01132-8"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2022.782579"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-51892-7.00010-3"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.62.2.314"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.4103\/JPN.JPN_8_18"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.52265","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T05:40:44Z","timestamp":1737438044000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.52265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,3]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/acn3.52265"],"URL":"https:\/\/doi.org\/10.1002\/acn3.52265","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"type":"print","value":"2328-9503"},{"type":"electronic","value":"2328-9503"}],"subject":[],"published":{"date-parts":[[2024,12,3]]},"assertion":[{"value":"2024-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}