Mikrolissenzephalie

Magnetic

resonance imaging (MRI) of two patients. a, b Patient A (p.N329S TUBA1A mutation) shows lissencephaly with cerebellar hypoplasia. Thin cerebral mantle and agyric cerebral cortices (arrow in figure a) are observed without an anterior-posterior gradient. The corpus callosum is not present (arrow in figure b). c, d Patient B (p.R264C TUBA1A mutation) shows pachygyria with a posterior-anterior gradient (arrow in figure c). Cerebellar and brain stem hypoplasia are not as clear as in Patient A (arrowhead in figure d). The corpus callous is present (arrow in figure d). e Schematic structure of TUBA1A is represented based on a previous report [34]. Both missense mutations in TUBA1A were located in the intermediate domain of TUBA1A. f Three-dimensional structure of the TUBA1A protein. Helices are presented as cylinders. The arrows show the residue of each mutation. The p.N329S mutation was located on alpha-helix H10, which formed the interface with beta-tubulin. The p.R264C mutation was located between alpha-helix H8 and the beta sheet, which could be responsible for providing stability to the tertiary structure