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In four cases, neuropathological assessments of the neuroaxis were performed. Genetic testing included short read whole genome sequencing, short tandem repeat analysis with ExpansionHunter de novo, and long read sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Novel features for SCA4 include dysautonomia, motor neuron affection, and abnormal eye movements. We found evidence of anticipation; neuroimaging demonstrated atrophy in the cerebellum, brainstem, and spinal cord. [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG\u2010PET demonstrated brain hypometabolism and [\n                      <jats:sup>11<\/jats:sup>\n                      C]Flumazenil\u2010PET reduced binding in several brain lobes, insula, thalamus, hypothalamus, and cerebellum. Moderate to severe loss of Purkinje cells in the cerebellum and of motor neurons in the anterior horns of the spinal cord along with pronounced degeneration of posterior tracts was also found. Intranuclear, mainly neuronal, inclusions positive for p62 and ubiquitin were sparse but widespread in the CNS. This finding prompted assessment for nucleotide expansions. A polyglycine stretch encoding GGC expansions in the last exon of the zink finger homeobox 3 gene was identified segregating with disease and not found in 1000 controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      SCA4 is a neurodegenerative disease caused by a novel GGC expansion in the coding region of\n                      <jats:italic>ZFHX3<\/jats:italic>\n                      , and its spectrum is expanded to include dysautonomia and neuromuscular manifestations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/joim.13815","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T02:55:05Z","timestamp":1720407305000},"page":"234-248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Spinocerebellar ataxia type 4 is caused by a GGC expansion in the\n                    <i>ZFHX3<\/i>\n                    gene and is associated with prominent dysautonomia and motor neuron signs"],"prefix":"10.1111","volume":"296","author":[{"given":"Martin","family":"Paucar","sequence":"first","affiliation":[{"name":"Department of Neurology Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Clinical Neuroscience Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital  Stockholm Sweden"},{"name":"Science for Life Laboratory Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm 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":"Jos\u00e9","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":"Cilla","family":"S\u00f6derh\u00e4ll","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health 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