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

Dev Med Child Neurol. 2012 Aug;54(8):765-9. doi: 10.1111/j.1469-8749.2012.04316.x. Epub 2012 May 16.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Axons / pathology
  • Brain / abnormalities*
  • Child
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Malformations of Cortical Development / diagnosis
  • Malformations of Cortical Development / genetics*
  • Malformations of Cortical Development / pathology
  • Microcephaly / genetics*
  • Mutation, Missense / genetics*
  • Tubulin / genetics*


  • Tubulin