Overlapping cortical malformations and mutations in TUBB2B and TUBA1A
Thomas D Cushion1, William B Dobyns, Jonathan G L Mullins
1Institute of Life Science, College of Medicine, Swansea University, Swansea SA2 8PP, UK.
Brain : a Journal of Neurology
|January 31, 2013
Summary
Mutations in tubulin genes cause brain malformations like polymicrogyria and lissencephaly, revealing a spectrum of cortical dysplasia and shared mechanisms in microtubule function.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Polymicrogyria and lissencephaly are heterogeneous cortical brain development disorders.
- While often single-gene, their etiology remains unknown in many cases.
- Tubulin gene mutations are linked to these disorders and associated anomalies.
Purpose of the Study:
- To investigate the role of TUBB2B and TUBA1A genes in polymicrogyria and lissencephaly.
- To identify mutations in these tubulin genes in patients with cortical malformations.
Main Methods:
- Sequencing of TUBB2B and TUBA1A coding regions in 47 polymicrogyria and 5 atypical lissencephaly patients.
- Analysis of identified mutations and associated phenotypes.
Main Results:
- Identified four β-tubulin and two α-tubulin mutations.
- Observed a spectrum of cortical and extra-cortical anomalies, with dysmorphic basal ganglia as a consistent feature.
- Found a TUBB2B mutation associated with lissencephaly and others with polymicrogyria-like dysplasia.
Conclusions:
- Cortical malformations associated with these tubulin genes represent a spectrum from lissencephaly to polymicrogyric dysplasia.
- Suggests shared pathogenic mechanisms involving microtubular function.
- Highlights tubulinopathies as a recognizable category of brain malformations.
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