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 > 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.
A novel mutation in the ß-tubulin gene TUBB2B associated with complex malformation of cortical development and deficits in axonal guidance / R. Romaniello, A. Tonelli, F. Arrigoni, C. Baschirotto, F. Triulzi, N. Bresolin, M. Bassi, R. Borgatti. - In: DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. - ISSN 0012-1622. - 54:8(2012 Aug), pp. 765-769.
A novel mutation in the ß-tubulin gene TUBB2B associated with complex malformation of cortical development and deficits in axonal guidance
F. Triulzi;N. Bresolin;
2012
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 a- and beta-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 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.File | Dimensione | Formato | |
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