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Interneuron, interrupted: molecular pathogenesis of ARX mutations and X-linked infantile spasms.

Abstract

X-linked Infantile Spasms Syndrome (ISSX) is a catastrophic epilepsy of early childhood with intractable seizures, intellectual disability, and poor prognosis. A spectrum of mutations in the Aristaless-Related Homeobox gene (ARX) has been linked to ISSX, and downstream targets of this interneuron-expressed transcription factor are being defined. Recent advances combining in vitro and in vivo methods have unveiled complex interactions between Arx and its binding partners and their effects on cell migration and maturation that can help explain the diversity of ARX phenotypes. New mutant mouse models of Arx-induced pathology, including a recent human triplet-repeat expansion mutation with a phenotype of infantile spasms and electrographic seizures, provide valuable tools for exploring the pathophysiology of Arx and substrates for testing novel therapies.

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  • Authors

    Olivetti PR, Noebels JL

    Source

    Current opinion in neurobiology 22:5 2012 Oct pg 859-65

    MeSH

    Aicardi Syndrome
    Animals
    Disease Models, Animal
    Homeodomain Proteins
    Humans
    Interneurons
    Mice
    Mutation
    Spasms, Infantile
    Transcription Factors

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    22565167