Loss-of-Function Mutations in FRRS1L Lead to an Epileptic-Dyskinetic Encephalopathy

Glutamatergic neurotransmission governs excitatory signaling in the mammalian brain, and abnormalities of glutamate signaling have been shown to contribute to both epilepsy and hyperkinetic movement disorders. The etiology of many severe childhood movement disorders and epilepsies remains uncharacterized. We describe a neurological disorder with epilepsy and prominent choreoathetosis caused by biallelic pathogenic variants in FRRS1L, which encodes an AMPA receptor outer-core protein. Loss of FRRS1L function attenuates AMPA-mediated currents, implicating chronic abnormalities of glutamatergic neurotransmission in this monogenic neurological disease of childhood

Legitimacy

Legitimacy has emerged as a pivotal but often confusing construct in management research. The popularity of the concept and its widespread application to so many theoretical and empirical contexts has layered the construct of legitimacy with considerable surplus meaning. The object of this paper is to bring clarity and theoretical discipline to an important but misunderstood construct. We demonstrate through a description of the historical evolution of the construct that legitimacy has evolved in three distinct ways; from a focus on the property elements of legitimacy, to a focus on the process of legitimacy construction and finally to a focus on the cognitive practices by which legitimacy is negotiated