{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:40:48Z","timestamp":1791225648263,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,12,6]],"date-time":"2015-12-06T00:00:00Z","timestamp":1449360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001209","name":"Knights Templar Eye Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001209","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["5K12NS049453\u201009"],"award-info":[{"award-number":["5K12NS049453\u201009"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>One set of missense mutations in the neuron specific beta tubulin isotype 3 (<jats:italic>TUBB3<\/jats:italic>) has been reported to cause malformations of cortical development (MCD), while a second set has been reported to cause isolated or syndromic Congenital Fibrosis of the Extraocular Muscles type 3 (CFEOM3). Because <jats:italic>TUBB3<\/jats:italic> mutations reported to cause CFEOM had not been associated with cortical malformations, while mutations reported to cause MCD had not been associated with CFEOM or other forms of paralytic strabismus, it was hypothesized that each set of mutations might alter microtubule function differently. Here, however, we report two novel de novo heterozygous TUBB3 amino acid substitutions, G71R and G98S, in four patients with both MCD and syndromic CFEOM3. These patients present with moderately severe CFEOM3, nystagmus, torticollis, and developmental delay, and have intellectual and social disabilities. Neuroimaging reveals defective cortical gyration, as well as hypoplasia or agenesis of the corpus callosum and anterior commissure, malformations of hippocampi, thalami, basal ganglia and cerebella, and brainstem and cranial nerve hypoplasia. These new TUBB3 substitutions meld the two previously distinct TUBB3\u2010associated phenotypes, and implicate similar microtubule dysfunction underlying both. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37362","type":"journal-article","created":{"date-parts":[[2015,12,7]],"date-time":"2015-12-07T04:38:17Z","timestamp":1449463097000},"page":"297-305","source":"Crossref","is-referenced-by-count":70,"title":["Two unique <i>TUBB3<\/i> mutations cause both CFEOM3 and malformations of cortical development"],"prefix":"10.1002","volume":"170","author":[{"given":"Mary C.","family":"Whitman","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Ophthalmology Harvard Medical School Boston Massachusetts"},{"name":"FM Kirby Neurobiology Center Boston Children's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Andrews","sequence":"additional","affiliation":[{"name":"FM Kirby Neurobiology Center Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Neurology Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Neurology Harvard Medical School Boston Massachusetts"},{"name":"Howard Hughes Medical Institute Chevy Chase Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai\u2010Man","family":"Chan","sequence":"additional","affiliation":[{"name":"FM Kirby Neurobiology Center Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Neurology Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Neurology Harvard Medical School Boston Massachusetts"},{"name":"Howard Hughes Medical Institute Chevy Chase Maryland"},{"name":"Program in Genomics Boston Children's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max A.","family":"Tischfield","sequence":"additional","affiliation":[{"name":"FM Kirby Neurobiology Center Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Neurology Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Neurology Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven F.","family":"Stasheff","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics (Neurology), Ophthalmology and Visual Sciences, Neurology and Biomedical Engineering University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Brancati","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral and Biotechnological Sciences Gabriele d'Annunzio University Chieti Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilma","family":"Ortiz\u2010Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Neurology Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Nuovo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention Tor Vergata University Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Garaci","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy Tor Vergata University Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"MacKinnon","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Boston Children's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Ophthalmology Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Ellen","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Radiology Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C.","family":"Engle","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Ophthalmology Harvard Medical School Boston Massachusetts"},{"name":"FM Kirby Neurobiology Center Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Neurology Boston Children's Hospital Boston Massachusetts"},{"name":"Department of Neurology Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.053"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu082"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds393"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.038"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws345"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/08820538.2013.825288"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/08820530701745181"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.5077"},{"key":"e_1_2_6_10_1","first-page":"1","article-title":"Recognisable cerebellar dysplasia associated with mutations in multiple tubulin genes","author":"Oegema R","year":"2015","journal-title":"Hum Mol Genet"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq377"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.12.011"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2011.01.003"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1261"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.123.9.1254"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37362","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37362","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T20:05:19Z","timestamp":1696622719000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,6]]},"references-count":14,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["10.1002\/ajmg.a.37362"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37362","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,6]]}}}