title: A novel mutation in the β-tubulin gene TUBB2B associated with complex malformation of cortical development and deficits in axonal guidance.
abstract: Neurological disorders characterized by abnormal neuronal migration, organization, axon guidance, and maintenance have recently been associated with missense and splice-site mutations in the genes encoding α- and β-tubulin isotypes TUBA1A, TUBB2B, TUBB3, and TUBA8. We found a novel heterozygous mutation c.419G > C in exon 4 of the gene encoding TUBB2B in a female with microcephaly, agenesis of the corpus callosum, open-lip schizencephaly of the left parietal lobe, extensive polymicrogyria, basal ganglia and thalami dysmorphisms, and vermis and right third nerve hypoplasia. The missense change results in a glycine to alanine substitution; the mutated residue falls within an invariant glycine-rich region and therefore is likely to result in impaired protein function and possibly microtubule formation. This study expands the spectrum of brain malformations associated with mutations in the β-tubulin gene TUBB2B, supporting its critical role in migration/organization and axon guidance processes. In addition, it suggests a possible genetic aetiology of schizencephaly, thus strengthening the hypothesis that there is a common pathophysiological base in polymicrogyria and schizencephaly.
authors.affiliation: Department of Child Neuropsychiatry, Eugenio Medea Scientific Institute, Bosisio Parini, Lecco, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Romaniello
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tonelli
authors.forename: Filippo
authors.initials: F
authors.lastname: Arrigoni
authors.forename: Cinzia
authors.initials: C
authors.lastname: Baschirotto
authors.forename: Fabio
authors.initials: F
authors.lastname: Triulzi
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bassi
authors.forename: Renato
authors.initials: R
authors.lastname: Borgatti
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D001369:Axons / Q000473:pathology; D001921:Brain / Q000002:abnormalities*; D002648:Child; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D054220:Malformations of Cortical Development / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008831:Microcephaly / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D014404:Tubulin / Q000235:genetics*
chemical_list: D014404:Tubulin