{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T05:22:36Z","timestamp":1777180956633,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T00:00:00Z","timestamp":1712361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S01165X\/1"],"award-info":[{"award-number":["MR\/S01165X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S005021\/1"],"award-info":[{"award-number":["MR\/S005021\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0601943"],"award-info":[{"award-number":["G0601943"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/V012177\/1"],"award-info":[{"award-number":["MR\/V012177\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Based on a limited number of reported families, biallelic <jats:italic>CA8<\/jats:italic> variants have currently been associated with a recessive neurological disorder named, cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CAMRQ\u20103).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We aim to comprehensively investigate <jats:italic>CA8<\/jats:italic>\u2010related disorders (<jats:italic>CA8<\/jats:italic>\u2010RD) by reviewing existing literature and exploring neurological, neuroradiological, and molecular observations in a cohort of newly identified patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the phenotype of 27 affected individuals from 14 families with biallelic <jats:italic>CA8<\/jats:italic> variants (including data from 15 newly identified patients from eight families), ages 4 to 35\u2009years. Clinical, genetic, and radiological assessments were performed, and zebrafish models with <jats:italic>ca8<\/jats:italic> knockout were used for functional analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients exhibited varying degrees of neurodevelopmental disorders (NDD), along with predominantly progressive cerebellar ataxia and pyramidal signs and variable bradykinesia, dystonia, and sensory impairment. Quadrupedal gait was present in only 10 of 27 patients. Progressive selective cerebellar atrophy, predominantly affecting the superior vermis, was a key diagnostic finding in all patients. Seven novel homozygous <jats:italic>CA8<\/jats:italic> variants were identified. Zebrafish models demonstrated impaired early neurodevelopment and motor behavior on <jats:italic>ca8<\/jats:italic> knockout.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our comprehensive analysis of phenotypic features indicates that <jats:italic>CA8<\/jats:italic>\u2010RD exhibits a wide range of clinical manifestations, setting it apart from other subtypes within the category of CAMRQ. <jats:italic>CA8<\/jats:italic>\u2010RD is characterized by cerebellar atrophy and should be recognized as part of the autosomal\u2010recessive cerebellar ataxias associated with NDD. Notably, the presence of progressive superior vermis atrophy serves as a valuable diagnostic indicator. \u00a9 2024 The Authors. <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.29754","type":"journal-article","created":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T03:33:15Z","timestamp":1712374395000},"page":"983-995","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Clinical and Molecular Spectrum of Autosomal Recessive <scp><i>CA8<\/i><\/scp>\u2010Related Cerebellar Ataxia"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-4010","authenticated-orcid":false,"given":"Rauan","family":"Kaiyrzhanov","sequence":"first","affiliation":[{"name":"Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology University College London  London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6320-2641","authenticated-orcid":false,"given":"Juan Dar\u00edo","family":"Ortigoza\u2010Escobar","sequence":"additional","affiliation":[{"name":"U\u2010703 Centre for Biomedical Research on Rare Diseases (CIBER\u2010ER), Instituto de Salud Carlos III  Barcelona Spain"},{"name":"Movement Disorders Unit, Pediatric Neurology Department, Institut de Recerca, Hospital Sant Joan de D\u00e9u Barcelona  Barcelona Spain"},{"name":"European Reference Network for Rare Neurological Diseases (ERN\u2010RND)  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4552-9736","authenticated-orcid":false,"given":"Brett W.","family":"Stringer","sequence":"additional","affiliation":[{"name":"Griffith Institute for Drug Discovery, Centre for Cellular Phenomics School of Environment and Science Griffith University  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manizha","family":"Ganieva","sequence":"additional","affiliation":[{"name":"Avicenna Tajik State Medical University Department of Neurology and Medical Genetics  Dushanbe Tajikistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1644-2212","authenticated-orcid":false,"given":"Vykuntaraju K.","family":"Gowda","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Indira Gandhi Institute of Child Health  Bangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varunvenkat M.","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Indira Gandhi Institute of Child Health  Bangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7998-4185","authenticated-orcid":false,"given":"Alfons","family":"Macaya","sequence":"additional","affiliation":[{"name":"European Reference Network for Rare Neurological Diseases (ERN\u2010RND)  Barcelona Spain"},{"name":"Department of Paediatric Neurology University Hospital Vall d'Hebron, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4596-7293","authenticated-orcid":false,"given":"Andreas","family":"Laner","sequence":"additional","affiliation":[{"name":"MGZ \u2010 Medical Genetics Centre  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enas","family":"Onbool","sequence":"additional","affiliation":[{"name":"Neurology department, King Abdulaziz Specialist Hospital  Skaka Aljouf Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randa","family":"Al\u2010Shammari","sequence":"additional","affiliation":[{"name":"Department of Medical Genomics Centre for Genomic Medicine, King Faisal Specialist Hospital and Research Centre  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Al\u2010Owain","sequence":"additional","affiliation":[{"name":"Department of Medical Genomics Centre for Genomic Medicine, King Faisal Specialist Hospital and Research Centre  Riyadh Saudi Arabia"},{"name":"College of Medicine Alfaisal University  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4284-6154","authenticated-orcid":false,"given":"Nicolas","family":"Deconinck","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies Neuromusculaires et Service de Neurologie P\u00e9diatrique, H\u00f4pital Universitaire des Enfants Reine Fabiola (HUDERF), H\u00f4pital Universitaire de Bruxelles (HUB) Universit\u00e9 Libre de Bruxelles (ULB)  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catheline","family":"Vilain","sequence":"additional","affiliation":[{"name":"Department of Genetics, H\u00f4pital Universitaire Reine Fabiola (HUDERF); H\u00f4pital Universitaire de Bruxelles (HUB) Universit\u00e9 Libre de Bruxelles (ULB)  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauline","family":"Dontaine","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies Neuromusculaires et Service de Neurologie P\u00e9diatrique, H\u00f4pital Universitaire des Enfants Reine Fabiola (HUDERF), H\u00f4pital Universitaire de Bruxelles (HUB) Universit\u00e9 Libre de Bruxelles (ULB)  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleanor","family":"Self","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology University College London  London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabia","family":"Akram","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology University College London  London United Kingdom"},{"name":"Neurochemical biology and Genetics Laboratory (NGL), Department of Physiology, Faculty of Life Sciences Government College University  Faisalabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9090-7789","authenticated-orcid":false,"given":"Ghulam","family":"Hussain","sequence":"additional","affiliation":[{"name":"Neurochemical biology and Genetics Laboratory (NGL), Department of Physiology, Faculty of Life Sciences Government College University  Faisalabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahid Mahmood","family":"Baig","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics Laboratory, Health Biotechnology Division National Institute for Biotechnology and Genetic Engineering (NIBGE) College  Faisalabad Pakistan"},{"name":"Department of Biological and Biomedical Sciences Aga Khan University  Karachi Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javed","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Neurology, Allied Hospital Faisalabad Medical University  Faisalabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0132-7921","authenticated-orcid":false,"given":"Vincenzo","family":"Salpietro","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology University College London  London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maedeh","family":"Neshatdoust","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology University of Isfahan  Isfahan Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahboubeh","family":"Kasiri","sequence":"additional","affiliation":[{"name":"School of Medicine Shahrekord University of Medical Sciences  Shahrekord Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1964-6306","authenticated-orcid":false,"given":"Gozde","family":"Yesil","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Istanbul University, Istanbul Faculty of Medicine  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Turkan","family":"Uygur","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Bezmialem Vakif University  \u0130stanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Pysden","sequence":"additional","affiliation":[{"name":"Paediatric Neurology Department Leeds Teaching Hospitals, Leeds General Infirmary  Leeds United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian R.","family":"Berry","sequence":"additional","affiliation":[{"name":"Yorkshire and North East Genomic Laboratory Hub Central Laboratory  Leeds United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cesar Augusto","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Radiology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2918-4689","authenticated-orcid":false,"given":"Jean","family":"Giacomotto","sequence":"additional","affiliation":[{"name":"Griffith Institute for Drug Discovery, Centre for Cellular Phenomics School of Environment and Science Griffith University  Brisbane Queensland Australia"},{"name":"Queensland Brain Institute The University of Queensland  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-7777","authenticated-orcid":false,"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology University College London  London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6763-1542","authenticated-orcid":false,"given":"Reza","family":"Maroofian","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology University College London  London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20030110"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000487"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.31227"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10423"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61805"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13666"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.73"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.126110.111"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.170"},{"issue":"2","key":"e_1_2_10_11_1","first-page":"258","article-title":"Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability","volume":"26","author":"Breuss MW","year":"2017","journal-title":"Hum Mol Genet"},{"issue":"3","key":"e_1_2_10_12_1","first-page":"1","article-title":"Neurodevelopmental syndrome with intellectual disability, speech impairment, and Quadrupedia is associated with glutamate Receptor Delta 2 gene defect","volume":"11","author":"Grigorenko AP","year":"2022","journal-title":"Cell"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21082764"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59683"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/g3journal\/jkab321"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds438"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-023-04879-5"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874205X01004010078"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207450500455330"},{"key":"e_1_2_10_20_1","first-page":"250","article-title":"Unertan syndrome a new theory on the evolution of human","volume":"4","author":"Tan U","year":"2005","journal-title":"Mind"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/RMR.0000000000000175"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.03.004"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0030108"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-67"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40673-015-0027-x"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00234-021-02682-2"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0543-7"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-023-01558-w"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2021.120020"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2014.04.017"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.29754","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T12:08:02Z","timestamp":1760962082000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.29754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,6]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/mds.29754"],"URL":"https:\/\/doi.org\/10.1002\/mds.29754","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,6]]},"assertion":[{"value":"2023-10-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}