title: A novel TUBB3 mutation in a sporadic patient with asymmetric cortical dysplasia.
abstract: Recent advances in molecular technology have led to the discovery of several genes related to human malformations of cortical development (MCDs). The beta-tubulin class III gene (TUBB3) was identified as a gene responsible for MCDs. Although mouse-model experiments have not revealed any findings of neuronal migration disorders, human TUBB3 mutations have been identified in patients with congenital fibrosis of the extraocular muscles. Since the discovery of a TUBB3 mutation, only 15 mutations have been identified. In this study, comprehensive mutation screening through next-generation sequencing identified a novel TUBB3 mutation (p.Ser230Leu) in a sporadic patient with moderate developmental delay associated with mild MCD. Compared to patients with the alpha-tubulin class 1a gene (TUBA1A) mutations, patients with TUBB3 mutations show milder phenotypic manifestations and milder MCD. Therefore, patients with milder MCD manifestations may be under-diagnosed, and TUBB3 mutations may be rarely identified. Additional genotype-phenotype information should be accumulated for further understanding of the TUBB3 functional relevance.
authors.affiliation: Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Japan.|Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D001921:Brain / Q000473:pathology; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D054220:Malformations of Cortical Development / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D014404:Tubulin / Q000235:genetics*
chemical_list: C498585:TUBB3 protein, human; D014404:Tubulin
keywords: beta-tubulin class III (TUBB3); malformation of cortical development (MCD); mutation; tubulin family