title: A patient with lissencephaly, developmental delay, and infantile spasms, due to de novo heterozygous mutation ofKIF2A.
abstract: BACKGROUND
  Microtubules are dynamic polymers ofα/βtubulin heterodimers that play a critical role in cerebral cortical development, by regulating neuronal migration, differentiation, and morphogenesis. Mutations in genes that encode eitherα- orβ-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 inEscherichia coliand HeLa cells.
  
  
  RESULTS
  The patient was found to have a novel de novo mutation in kinesin family member 2A (KIF2A). 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.
  
  
  CONCLUSIONS
  Findings support the pathogenic link betweenKIF2Amutation and lissencephaly, and expand the range of presentation to include infantile spasms and congenital anomalies.
authors.affiliation: Department of Molecular Pharmacology and Biochemistry New York University Langone Medical center New York New York 10016.
authors.forename: Guoling
authors.initials: G
authors.lastname: Tian
authors.affiliation: Department of Pediatrics Division of Neurology The Children's Hospital of Philadelphia Philadelphia Pennsylvania 19104.
authors.forename: Ana G
authors.initials: AG
authors.lastname: Cristancho
authors.affiliation: Department of Pediatrics Division of Neurology The Children's Hospital of Philadelphia Philadelphia Pennsylvania 19104.
authors.forename: Holly A
authors.initials: HA
authors.lastname: Dubbs
authors.affiliation: Neuro-Opthalmology ServiceDivision of OphthalmologyThe Children's Hospital of PhiladelphiaPhiladelphiaPennsylvania19104; Department of NeurologyThe Perelman School of Medicine at The University of PennsylvaniaPhiladelphiaPennsylvania19104.
authors.forename: Grant T
authors.initials: GT
authors.lastname: Liu
authors.affiliation: Department of Molecular Pharmacology and Biochemistry New York University Langone Medical center New York New York 10016.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Cowan
authors.affiliation: Department of PediatricsDivision of NeurologyThe Children's Hospital of PhiladelphiaPhiladelphiaPennsylvania19104; Department of NeurologyThe Perelman School of Medicine at The University of PennsylvaniaPhiladelphiaPennsylvania19104; Department of NeuroscienceThe Perelman School of Medicine at The University of PennsylvaniaPhiladelphiaPennsylvania19104.
authors.forename: Ethan M
authors.identifier: 0000-0002-7404-735X
authors.initials: EM
authors.lastname: Goldberg
keywords: Brain development; KIF2A; lissencephaly; microtubules