Chapter

Rare Genetic Causes of Lissencephaly May Implicate Microtubule-Based Transport in the Pathogenesis of Cortical Dysplasias

Judy S. Liu, Christian R. Schubert and Christopher A. Walsh

in Jasper's Basic Mechanisms of the Epilepsies

Fourth edition

Published on behalf of ©Jeffrey L. Noebels, Massimo Avoli, Michael A. Rogawski, Richard W. Olsen, and Antonio V. Delgado-Escueta

Published in print July 2012 | ISBN: 9780199746545
Published online April 2013 | e-ISBN: 9780199322817 | DOI: http://dx.doi.org/10.1093/med/9780199746545.003.0060

Series: Contemporary Neurology Series

Rare Genetic Causes of Lissencephaly May Implicate Microtubule-Based Transport in the Pathogenesis of Cortical Dysplasias

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Disruption of early neural development can cause severe forms of mental retardation and epilepsy associated with defects in cortical structure, such as lissencephaly (“smooth brain”), a disorder resulting from abnormal neuronal migration. Of the six causative genes for classical lissencephaly, three—LIS1, DCX, and TUBA1A—encode for microtubule-related proteins, indicating the importance of this pathway for neuronal migration (Table 60–1). The lissencephaly 1 (LIS1) protein is an adaptor for dynein, a microtubule motor protein.1 Doublecortin (DCX) encodes a microtubule-associated protein (MAP).2,3 Finally, tubulin α1a (TUBA1A) is a gene that encodes an α-tubulin subunit that is enriched during brain development.4 These lissencephalic syndromes clinically all share a widespread disruption of lamination in the cerebral cortex (Fig. 60–1). Since all three genes appear to regulate microtubule-based transport, their functional relation and regulation during development is an area of active investigation with implications that may be significant for a wider cohort of patients with focal cortical dysplasias. Cortical dysplasias are a common cause of refractory epilepsy and share some of the histological features of lissencephaly, including the dyslamination and abnormal neuronal morphology.5 Disruption of microtubule-based pathways may lead to cortical dysplasias, and the causative genes for lissencephaly are a starting point for further investigation.

Chapter.  8057 words.  Illustrated.

Subjects: Neurology

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