Complex cortical malformations associated with mutations in tubulin genes: TUBA1A, TUBA8, TUBB2B, TUBB3, TUBB5 and TUBG1 commonly referred to as tubulinopathies, are a heterogeneous group of conditions with a wide spectrum of clinical severity.
Three de novo missense TUBA1A mutations were identified in three unrelated patients with PMG representing 3.1% of PMG and 10% of PMGs with complex cerebral malformations.
All together, it emerges that the TUBA1A related lissencephaly spectrum ranges from perisylvian pachygyria, in the less severe form, to posteriorly predominant pachygyria in the most severe, associated with dysgenesis of the anterior limb of the internal capsule and mild to severe cerebellar hypoplasia.
Mutations in the alpha-1a Tubulin (TUBA1A) gene have recently been found to cause cortical malformations resemblant of classical lissencephaly but with a specific combination of features.
Neuroanatomical similarities between the Tuba1a mutant mouse and mice deficient for Doublecortin (Dcx) and Lis1 genes, and the well-established functional interaction between DCX and microtubules (MTs), led us to hypothesize that mutations in TUBA1A (TUBA3, previous symbol), the human homolog of Tuba1a, might give rise to cortical malformations.