Figure 6.

Mutations in TUBA3 Cause Lissencephaly in Humans

Screening of lissencephalic patients without mutations in DCX or LIS1 identified two individuals with spontaneous pathogenic mutations in TUBA3.

(A and B) The sequencing traces for the father (♂), mother (♀), and affected patient (P) for these two individuals. In the first, a C to T substitution mutates an arginine residue to histidine (R402H), and, in the second, a G to A substitution mutates another arginine to cysteine (R264C).

(C–E) The R402H patient shows severe lissencephaly.

(F–H) The second individual exhibits less severe cortical abnormalities.

(I and J) Both these residues are highly conserved in different species and isotypes of α-tubulin.