{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:39:03Z","timestamp":1791607143641,"version":"4.3.4"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T00:00:00Z","timestamp":1533600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>The TUBA1A gene encodes tubulin alpha-1A, a protein that is highly expressed in the fetal brain. Alpha- and beta-tubulin subunits form dimers, which then co-assemble into microtubule polymers: dynamic, scaffold-like structures that perform key functions during neurogenesis, neuronal migration, and cortical organisation. Mutations in TUBA1A have been reported to cause a range of brain malformations. We describe four unrelated patients with the same de novo missense mutation in TUBA1A, c.5G&gt;A, p.(Arg2His), as found by next generation sequencing. Detailed comparison revealed similar brain phenotypes with mild variability. Shared features included developmental delay, microcephaly, hypoplasia of the cerebellar vermis, dysplasia or thinning of the corpus callosum, small pons, and dysmorphic basal ganglia. Two of the patients had bilateral perisylvian polymicrogyria. We examined the effects of the p.(Arg2His) mutation by computer-based protein structure modelling and heterologous expression in HEK-293 cells. The results suggest the mutation subtly impairs microtubule function, potentially by affecting inter-dimer interaction. Based on its sequence context, c.5G&gt;A is likely to be a common recurrent mutation. We propose that the subtle functional effects of p.(Arg2His) may allow for other factors (such as genetic background or environmental conditions) to influence phenotypic outcome, thus explaining the mild variability in clinical manifestations.<\/jats:p>","DOI":"10.3390\/brainsci8080145","type":"journal-article","created":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T11:20:23Z","timestamp":1533640823000},"page":"145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Clinical and Functional Characterization of the Recurrent TUBA1A p.(Arg2His) Mutation"],"prefix":"10.3390","volume":"8","author":[{"given":"Jennifer F.","family":"Gardner","sequence":"first","affiliation":[{"name":"Institute of Medical Genetics, University Hospital of Wales, Cardiff CF14 4XW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0040-0069","authenticated-orcid":false,"given":"Thomas D.","family":"Cushion","sequence":"additional","affiliation":[{"name":"Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Niotakis","sequence":"additional","affiliation":[{"name":"Paediatrics Department, Venizelion Hospital, Knossos Ave, P.O. Box 44, Heraklion, 714 09 Crete, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather E.","family":"Olson","sequence":"additional","affiliation":[{"name":"Epilepsy Genetics Program, Department of Neurology, Division of Epilepsy and Clinical Neurophysiology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Ellen","family":"Grant","sequence":"additional","affiliation":[{"name":"Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H.","family":"Scott","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London WC1N 3JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Stoodley","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, North Bristol NHS Trust, Frenchay Hospital, Bristol BS16 1LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie S.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Division of Neurogenetics, Hugo W. Moser Research Institute, Kennedy Krieger Institute, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakkubai","family":"Naidu","sequence":"additional","affiliation":[{"name":"Division of Neurogenetics, Hugo W. Moser Research Institute, Kennedy Krieger Institute, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, The Johns Hopkins Hospital, Baltimore, Maryland, MD 21287, USA"},{"name":"Department of Pediatrics, The Johns Hopkins Hospital, Baltimore, Maryland, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Attie-Bitach","sequence":"additional","affiliation":[{"name":"Unit\u00e9 d\u2019Embryof\u0153topathologie, Service d\u2019Histologie Embryologie Cytog\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants Malades, Assistance Publique H\u00f4pitaux de Paris (APHP), 75004 Paris, France"},{"name":"Institut Imagine, INSERM U1163, Universit\u00e9 Paris Descartes, Sorbonne Paris Cite, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryse","family":"Bonni\u00e8res","sequence":"additional","affiliation":[{"name":"Unit\u00e9 d\u2019Embryof\u0153topathologie, Service d\u2019Histologie Embryologie Cytog\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants Malades, Assistance Publique H\u00f4pitaux de Paris (APHP), 75004 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucile","family":"Boutaud","sequence":"additional","affiliation":[{"name":"Unit\u00e9 d\u2019Embryof\u0153topathologie, Service d\u2019Histologie Embryologie Cytog\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants Malades, Assistance Publique H\u00f4pitaux de Paris (APHP), 75004 Paris, France"},{"name":"Institut Imagine, INSERM U1163, Universit\u00e9 Paris Descartes, Sorbonne Paris Cite, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e9recht\u00e9","family":"Encha-Razavi","sequence":"additional","affiliation":[{"name":"Unit\u00e9 d\u2019Embryof\u0153topathologie, Service d\u2019Histologie Embryologie Cytog\u00e9n\u00e9tique, H\u00f4pital Necker-Enfants Malades, Assistance Publique H\u00f4pitaux de Paris (APHP), 75004 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila M.","family":"Palmer-Smith","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, University Hospital of Wales, Cardiff CF14 4XW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hood","family":"Mugalaasi","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, University Hospital of Wales, Cardiff CF14 4XW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan G. L.","family":"Mullins","sequence":"additional","affiliation":[{"name":"Institute of Life Science, Swansea University Medical School, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela T.","family":"Pilz","sequence":"additional","affiliation":[{"name":"Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"},{"name":"Department of Clinical Genetics, West of Scotland Regional Genetics Service, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9778-6924","authenticated-orcid":false,"given":"Andrew E.","family":"Fry","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, University Hospital of Wales, Cardiff CF14 4XW, UK"},{"name":"Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7319","DOI":"10.1523\/JNEUROSCI.14-12-07319.1994","article-title":"The T alpha 1 alpha-tubulin promoter specifies gene expression as a function of neuronal growth and regeneration in transgenic mice","volume":"14","author":"Gloster","year":"1994","journal-title":"J. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/(SICI)1096-9861(19961007)374:1<52::AID-CNE4>3.0.CO;2-M","article-title":"Comparison of the expression of a T alpha 1:nlacZ transgene and T alpha 1 alpha-tubulin mRNA in the mature central nervous system","volume":"374","author":"Bamji","year":"1996","journal-title":"J. Comp. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cell.2006.12.017","article-title":"Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans","volume":"128","author":"Keays","year":"2007","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1212\/WNL.0b013e31821043f5","article-title":"TUBA1A mutations: from isolated lissencephaly to familial polymicrogyria","volume":"76","author":"Jansen","year":"2011","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1093\/brain\/aws338","article-title":"Overlapping cortical malformations and mutations in TUBB2B and TUBA1A","volume":"136","author":"Cushion","year":"2013","journal-title":"Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1093\/brain\/awu082","article-title":"The wide spectrum of tubulinopathies: what are the key features for the diagnosis?","volume":"137","author":"Poirier","year":"2014","journal-title":"Brain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nature10945","article-title":"De novo mutations revealed by whole-exome sequencing are strongly associated with autism","volume":"485","author":"Sanders","year":"2012","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/ejhg.2013.93","article-title":"Rare copy number variation in cerebral palsy","volume":"22","author":"McMichael","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15165","DOI":"10.1038\/srep15165","article-title":"TUBA1A mutation can cause a hydranencephaly-like severe form of cortical dysgenesis","volume":"5","author":"Yokoi","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/ng.380","article-title":"Mutations in the beta-tubulin gene TUBB2B result in asymmetrical polymicrogyria","volume":"41","author":"Jaglin","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.cell.2009.12.011","article-title":"Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance","volume":"140","author":"Tischfield","year":"2010","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4462","DOI":"10.1093\/hmg\/ddq377","article-title":"Mutations in the neuronal \u03b2-tubulin subunit TUBB3 result in malformation of cortical development and neuronal migration defects","volume":"19","author":"Poirier","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1016\/j.celrep.2012.11.017","article-title":"Mutations in the \u03b2-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities","volume":"2","author":"Breuss","year":"2012","journal-title":"Cell Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.ajhg.2014.03.009","article-title":"De novo mutations in the beta-tubulin gene TUBB2A cause simplified gyral patterning and infantile-onset epilepsy","volume":"94","author":"Cushion","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/ng.2613","article-title":"Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly","volume":"45","author":"Poirier","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5080","DOI":"10.1007\/s00330-017-4945-2","article-title":"Tubulin-related cerebellar dysplasia: definition of a distinct pattern of cerebellar malformation","volume":"27","author":"Romaniello","year":"2017","journal-title":"Eur. Radiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1093\/hmg\/ddq182","article-title":"TUBA1A mutations cause wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronal migration pathways converge on alpha tubulins","volume":"19","author":"Kumar","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1136\/jmg.2008.058073","article-title":"Refinement of cortical dysgeneses spectrum associated with TUBA1A mutations","volume":"45","author":"Poirier","year":"2008","journal-title":"J. Med. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1002\/humu.20572","article-title":"Large spectrum of lissencephaly and pachygyria phenotypes resulting from de novo missense mutations in tubulin alpha 1A (TUBA1A)","volume":"28","author":"Poirier","year":"2007","journal-title":"Hum. Mutat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1091\/mbc.e07-09-0861","article-title":"A pachygyria-causing alpha-tubulin mutation results in inefficient cycling with CCT and a deficient interaction with TBCB","volume":"19","author":"Tian","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/gim.2014.154","article-title":"Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions","volume":"17","author":"Farwell","year":"2015","journal-title":"Genet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/bdra.23472","article-title":"Clinical, genetic and neuropathological findings in a series of 138 fetuses with a corpus callosum malformation","volume":"106","author":"Alby","year":"2016","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/ana.24251","article-title":"Clinical whole exome sequencing in child neurology practice","volume":"76","author":"Srivastava","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1002\/ajmg.a.38684","article-title":"Novel de novo ZBTB20 mutations in three cases with Primrose syndrome and constant corpus callosum anomalies","volume":"176","author":"Alby","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/bdr2.1154","article-title":"In utero ultrasound diagnosis of corpus callosum agenesis leading to the identification of orofaciodigital type 1 syndrome in female fetuses","volume":"110","author":"Alby","year":"2018","journal-title":"Birth Defects Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/B978-0-12-394287-6.00005-7","article-title":"Structural modelling pipelines in next generation sequencing projects","volume":"89","author":"Mullins","year":"2012","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1126\/science.1230582","article-title":"Molecular mechanism of action of microtubule-stabilizing anticancer agents","volume":"339","author":"Prota","year":"2013","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1083\/jcb.201007081","article-title":"Template-free 13-protofilament microtubule-MAP assembly visualized at 8 A resolution","volume":"191","author":"Fourniol","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5.6.1","DOI":"10.1002\/cpbi.3","article-title":"Comparative Protein Structure Modeling Using MODELLER","volume":"54","author":"Webb","year":"2016","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_31","unstructured":"(2018, July 23). UCSF Chimera Home Page. Available online: https:\/\/www.cgl.ucsf.edu\/chimera\/."},{"key":"ref_32","unstructured":"(2018, July 23). Ensembl Genome Browser 93. Available online: http:\/\/www.ensembl.org\/index.html."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/ng.3511","article-title":"An expanded sequence context model broadly explains variability in polymorphism levels across the human genome","volume":"48","author":"Aggarwala","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/humu.20654","article-title":"Improving sequence variant descriptions in mutation databases and literature using the Mutalyzer sequence variation nomenclature checker","volume":"29","author":"Wildeman","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_35","unstructured":"(2018, July 23). Mutalyzer 2.0.28\u2014Welcome to the Mutalyzer Website. Available online: https:\/\/www.mutalyzer.nl\/."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5313","DOI":"10.1093\/hmg\/ddv250","article-title":"Recognizable cerebellar dysplasia associated with mutations in multiple tubulin genes","volume":"24","author":"Oegema","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/ejhg.2012.195","article-title":"Expanding the spectrum of TUBA1A-related cortical dysgenesis to Polymicrogyria","volume":"21","author":"Poirier","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s10072-014-1662-3","article-title":"DTI tractography of lissencephaly caused by TUBA1A mutation","volume":"35","author":"Kamiya","year":"2014","journal-title":"Neurol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1177\/0883073811436326","article-title":"Lissencephaly and band heterotopia: LIS1, TUBA1A, and DCX mutations in Hungary","volume":"27","author":"Bereg","year":"2012","journal-title":"J. Child Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1399-0004.2008.01093.x","article-title":"Refining the phenotype of alpha-1a Tubulin (TUBA1A) mutation in patients with classical lissencephaly","volume":"74","author":"Najm","year":"2008","journal-title":"Clin. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1056\/NEJMoa1510791","article-title":"Mutations in TUBB8 and Human Oocyte Meiotic Arrest","volume":"374","author":"Feng","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1093\/humrep\/dew322","article-title":"Novel mutations and structural deletions in TUBB8: Expanding mutational and phenotypic spectrum of patients with arrest in oocyte maturation, fertilization or early embryonic development","volume":"32","author":"Chen","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.rbmo.2017.05.017","article-title":"Mutation analysis of the TUBB8 gene in nine infertile women with oocyte maturation arrest","volume":"35","author":"Huang","year":"2017","journal-title":"Reprod. Biomed. Online"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/ana.23829","article-title":"Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene","volume":"73","author":"Lohmann","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1002\/ana.23832","article-title":"Mutations in the autoregulatory domain of \u03b2-tubulin 4a cause hereditary dystonia","volume":"73","author":"Hersheson","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1093\/brain\/awu110","article-title":"Hypomyelination with atrophy of the basal ganglia and cerebellum: further delineation of the phenotype and genotype-phenotype correlation","volume":"137","author":"Hamilton","year":"2014","journal-title":"Brain"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1212\/WNL.0000000000000535","article-title":"Expanding the phenotypic spectrum of TUBB4A-associated hypomyelinating leukoencephalopathies","volume":"82","author":"Miyatake","year":"2014","journal-title":"Neurology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.ajhg.2013.03.018","article-title":"A de novo mutation in the \u03b2-tubulin gene TUBB4A results in the leukoencephalopathy hypomyelination with atrophy of the basal ganglia and cerebellum","volume":"92","author":"Simons","year":"2013","journal-title":"Am. J. Hum. Genet."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/8\/8\/145\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:17:07Z","timestamp":1760195827000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/8\/8\/145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,7]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2018,8]]}},"alternative-id":["brainsci8080145"],"URL":"https:\/\/doi.org\/10.3390\/brainsci8080145","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,7]]}}}