A novel mutation in the beta-tubulin gene TUBB2B associated with complex malformation of cortical development and deficits in axonal guidance

作者:Romaniello Romina; Tonelli Alessandra; Arrigoni Filippo; Baschirotto Cinzia; Triulzi Fabio; Bresolin Nereo; Bassi Maria Teresa; Borgatti Renato*
来源:Developmental Medicine and Child Neurology, 2012, 54(8): 765-769.
DOI:10.1111/j.1469-8749.2012.04316.x

摘要

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 a- and beta-tubulin isotypes TUBA1A, TUBB2B, TUBB3, and TUBA8. We found a novel heterozygous mutation c.419G %26gt; 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 beta-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.

  • 出版日期2012-8