A patient with lissencephaly, developmental delay, and infantile spasms, due to de novo heterozygous mutation of .

BACKGROUND

Microtubules are dynamic polymers of / tubulin heterodimers that play a critical role in cerebral cortical development, by regulating neuronal migration, differentiation, and morphogenesis. Mutations in genes that encode either - or -tubulin or a spectrum of proteins involved in the regulation of microtubule dynamics lead to clinically devastating malformations of cortical development, including lissencephaly.

METHODS

This is a single case report or a patient with lissencephaly, developmental delay, nystagmus, persistent hyperplastic primary vitreous, and infantile spasms, and undertook a neurogenetic workup. We include studies of mutant function in and HeLa cells.

RESULTS

The patient was found to have a novel de novo mutation in kinesin family member 2A (). This mutation results in a substitution of isoleucine at a highly conserved threonine residue within the ATP-binding domain. The KIF2A p.Thr320Ile mutant protein exhibited abnormal solubility, and KIF2A p.Thr320Ile overexpression in cultured cells led to the formation of aberrant microtubule networks.

CONCLUSION

Findings support the pathogenic link between mutation and lissencephaly, and expand the range of presentation to include infantile spasms and congenital anomalies.