{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T18:19:23Z","timestamp":1788027563048,"version":"build-2784847793"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008084","name":"Neurof\u00f6rbundet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008084","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009389","name":"Stiftelsen Promobilia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009389","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":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Pathogenic variants in B\u2010cell receptor\u2010associated protein (<jats:italic>BCAP31)<\/jats:italic> are associated with X\u2010linked, deafness, dystonia and cerebral hypomyelination (DDCH) syndrome. DDCH is congenital and non\u2010progressive, featuring severe intellectual disability (ID), variable dysmorphism, and sometimes associated with shortened survival. <jats:italic>BCAP31<\/jats:italic> encodes one of the most abundant chaperones, with several functions including acting as a negative regulator of endoplasmic reticulum (ER) calcium ion (Ca<jats:sup>2+<\/jats:sup>) concentration. Here, we characterize an X\u2010linked syndrome, its underlying genotype, and a functional evaluation of the identified candidate genetic variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Evaluation of motor features, neuroimaging studies, neurophysiological, and cognitive tests. Whole exome sequencing (WES) was applied, a plasmid encoding <jats:italic>BCAP31<\/jats:italic> with and without a candidate variant was transfected into SH\u2010SY5Y cells to assess subcellular location and to measure Ca<jats:sup>2+<\/jats:sup> levels in the cytoplasm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Adult\u2010onset ataxia, cognitive impairment, and hearing loss leading to deafness are the predominant features. Reduced penetrance, slow progression with preserved ability to walk in advance age, and universal cerebellar atrophy are other features for this syndrome. This condition is associated with the new variant c.22G&gt;A (V8I) in <jats:italic>BCAP31<\/jats:italic> at Xq28. The subcellular location of the V8I BCAP31 protein was not altered but caused significant elevation of cytosolic Ca<jats:sup>2+<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings expand the spectrum of variants in <jats:italic>BCAP31<\/jats:italic> from neurodevelopmental syndromes to include a progressive neurodegenerative disease with variable expressivity. This is the first time ataxia is described in association with a <jats:italic>BCAP31<\/jats:italic> variant and functional evidence of pathogenicity is provided. Additional <jats:italic>BCAP31<\/jats:italic> cases featuring ataxia are needed to establish an association. \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.30116","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T08:24:28Z","timestamp":1737361468000},"page":"672-682","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["An X\u2010Linked Ataxia Syndrome in a Family with Hearing Loss Associated with a Novel Variant in the <scp><i>BCAP31<\/i><\/scp> Gene"],"prefix":"10.1002","volume":"40","author":[{"given":"Martin","family":"Paucar","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Neurology Karolinska University Hospital  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M.","family":"Laffita\u2010Mesa","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Neurobiology Care Sciences and Society, Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Nordgren","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Clinical Genetics and Genomics Sahlgrenska University Hospital  Gothenburg Sweden"},{"name":"Institute of Biomedicine, Department of Laboratory Medicine University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Engvall","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"},{"name":"Centre for Inherited Metabolic Diseases Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Uhl\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Lagerstedt\u2010Robinson","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6727-3802","authenticated-orcid":false,"given":"Per","family":"Svenningsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Karolinska Institutet  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