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A novel mutation in the β‐tubulin gene TUBB2B associated with complex malformation of cortical development and deficits in axonal guidance
Author(s) -
ROMANIELLO ROMINA,
TONELLI ALESSANDRA,
ARRIGONI FILIPPO,
BASCHIROTTO CINZIA,
TRIULZI FABIO,
BRESOLIN NEREO,
BASSI MARIA TERESA,
BORGATTI RENATO
Publication year - 2012
Publication title -
developmental medicine and child neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.658
H-Index - 143
eISSN - 1469-8749
pISSN - 0012-1622
DOI - 10.1111/j.1469-8749.2012.04316.x
Subject(s) - schizencephaly , polymicrogyria , lissencephaly , missense mutation , agenesis of the corpus callosum , biology , pachygyria , exon , neuroscience , genetics , corpus callosum , mutation , epilepsy , gene
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.