{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:55:37Z","timestamp":1789829737976,"version":"4.0.1"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,12,27]],"date-time":"2014-12-27T00:00:00Z","timestamp":1419638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recently, mutations in the <jats:italic>TUBB4A<\/jats:italic> gene have been found to underlie hypomyelination with atrophy of the basal ganglia and cerebellum (H\u2010ABC) syndrome, a rare neurodegenerative disorder of infancy and childhood. <jats:italic>TUBB4A<\/jats:italic> mutations also have been described as causative of DYT4 (\u201chereditary whispering dysphonia\u201d). However, in DYT4, brain imaging has been reported to be normal and, therefore, H\u2010ABC syndrome and DYT4 have been construed to be different disorders, despite some phenotypic overlap. Hence, the question of whether these disorders reflect variable expressivity or pleiotropy of <jats:italic>TUBB4A<\/jats:italic> mutations has been raised. We report four unrelated patients with imaging findings either partially or totally consistent with H\u2010ABC syndrome, who were found to have <jats:italic>TUBB4A<\/jats:italic> mutations. All four subjects had a relatively homogenous phenotype characterized by severe generalized dystonia with superimposed pyramidal and cerebellar signs, and also bulbar involvement leading to complete aphonia and swallowing difficulties, even though one of the cases had an intermediate phenotype between H\u2010ABC syndrome and DYT4. Genetic analysis of the <jats:italic>TUBB4A<\/jats:italic> gene showed one previously described and two novel mutations (c.941C&gt;T; p.Ala314Val and c.900G&gt;T; p.Met300Ile) in the exon 4 of the gene. While expanding the genetic spectrum of H\u2010ABC syndrome, we confirm its radiological heterogeneity and demonstrate that phenotypic overlap with DYT4. Moreover, reappraisal of previously reported cases would also argue against pleiotropy of <jats:italic>TUBB4A<\/jats:italic> mutations. We therefore suggest that H\u2010ABC and DYT4 belong to a continuous phenotypic spectrum associated with <jats:italic>TUBB4A<\/jats:italic> mutations. \u00a9 2014 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.26129","type":"journal-article","created":{"date-parts":[[2014,12,27]],"date-time":"2014-12-27T11:40:50Z","timestamp":1419680450000},"page":"828-833","source":"Crossref","is-referenced-by-count":53,"title":["H\u2010ABC syndrome and DYT4: Variable expressivity or pleiotropy of TUBB4 mutations?"],"prefix":"10.1002","volume":"30","author":[{"given":"Roberto","family":"Erro","sequence":"first","affiliation":[{"name":"Sobell Department of Motor Neuroscience and Movement Disorders University College London (UCL) Institute of Neurology  London United Kingdom"},{"name":"Dipartimento di Scienze Neurologiche e del Movimento Universit\u00e0 di Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Hersheson","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroscience UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Ganos","sequence":"additional","affiliation":[{"name":"Sobell Department of Motor Neuroscience and Movement Disorders University College London (UCL) Institute of Neurology  London United Kingdom"},{"name":"University Medical Center Hamburg\u2010Eppendorf (UKE) Neurology Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niccol\u00f3 E.","family":"Mencacci","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroscience UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Stamelou","sequence":"additional","affiliation":[{"name":"Sobell Department of Motor Neuroscience and Movement Disorders University College London (UCL) Institute of Neurology  London United Kingdom"},{"name":"Second Department of Neurology Kapodistrian University of Athens  Greece"},{"name":"Neurology Clinic Philipps University  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Batla","sequence":"additional","affiliation":[{"name":"Sobell Department of Motor Neuroscience and Movement Disorders University College London (UCL) Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie Catherine","family":"Thust","sequence":"additional","affiliation":[{"name":"The Lysholm Department of Neuroradiology National Hospital for Neurology and Neurosurgery  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose M.","family":"Bras","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroscience UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita J.","family":"Guerreiro","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroscience UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hardy","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroscience UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niall P.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Sobell Department of Motor Neuroscience and Movement Disorders University College London (UCL) Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroscience UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailash P.","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Sobell Department of Motor Neuroscience and Movement Disorders University College London (UCL) Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,27]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"1466","article-title":"New syndrome characterized by hypomyelination with atrophy of the basal ganglia and 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