{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T14:25:56Z","timestamp":1781360756809,"version":"3.54.1"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T00:00:00Z","timestamp":1581984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Finalizzata NET-2013-02356160"],"award-info":[{"award-number":["Ricerca Finalizzata NET-2013-02356160"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tubulinopathies are rare neurological disorders caused by alterations in tubulin structure and function, giving rise to a wide range of brain abnormalities involving neuronal proliferation, migration, differentiation and axon guidance. TUBB is one of the ten \u03b2-tubulin encoding genes present in the human genome and is broadly expressed in the developing central nervous system and the skin. Mutations in TUBB are responsible for two distinct pathological conditions: the first is characterized by microcephaly and complex structural brain malformations and the second, also known as \u201ccircumferential skin creases Kunze type\u201d (CSC-KT), is associated to neurological features, excess skin folding and growth retardation. We used a combination of immunocytochemical and cellular approaches to explore, on patients\u2019 derived fibroblasts, the functional consequences of two TUBB variants: the novel mutation (p.N52S), associated with basal ganglia and cerebellar dysgenesis, and the previously reported variant (p.M73T), linked to microcephaly, corpus callosum agenesis and CSC-KT skin phenotype. Our results demonstrate that these variants impair microtubule (MT) function and dynamics. Most importantly, our studies show an altered epidermal growth factor (EGF) and transferrin (Tf) intracellular vesicle trafficking in both patients\u2019 fibroblasts, suggesting a specific role of TUBB in MT-dependent vesicular transport.<\/jats:p>","DOI":"10.3390\/ijms21041385","type":"journal-article","created":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T04:06:01Z","timestamp":1582085161000},"page":"1385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["TUBB Variants Underlying Different Phenotypes Result in Altered Vesicle Trafficking and Microtubule Dynamics"],"prefix":"10.3390","volume":"21","author":[{"given":"Antonella","family":"Sferra","sequence":"first","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disorders, Department Neurosciences, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3249-0003","authenticated-orcid":false,"given":"Stefania","family":"Petrini","sequence":"additional","affiliation":[{"name":"Confocal Microscopy Core Facility, Research Laboratories, Ospedale Pediatrico Bambino Ges\u00f9, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-849X","authenticated-orcid":false,"given":"Emanuele","family":"Bellacchio","sequence":"additional","affiliation":[{"name":"Department of Research Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5612-821X","authenticated-orcid":false,"given":"Francesco","family":"Nicita","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disorders, Department Neurosciences, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Scibelli","sequence":"additional","affiliation":[{"name":"Unit of Child Neuropsychiatry, Department of Neurosciences, Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9505-5906","authenticated-orcid":false,"given":"Maria Lisa","family":"Dentici","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2197-9417","authenticated-orcid":false,"given":"Paolo","family":"Alfieri","sequence":"additional","affiliation":[{"name":"Unit of Child Neuropsychiatry, Department of Neurosciences, Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Cestra","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology (IBPM), National Research Council (CNR) and University of Rome \u201cSapienza\u201d, Department of Biology and Biotechnology, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-4590","authenticated-orcid":false,"given":"Enrico Silvio","family":"Bertini","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disorders, Department Neurosciences, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6367-1843","authenticated-orcid":false,"given":"Ginevra","family":"Zanni","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disorders, Department Neurosciences, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"key":"ref_1","first-page":"2","article-title":"Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly","volume":"25","year":"2014","journal-title":"Acta Neuropathol. 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