A Novel de novo Mutation in ATP1A3 and Childhood-onset Schizophrenia

Published in Molecular Case Studies, 2016

We describe a child with onset of command auditory hallucinations and behavioral regression at 6 yr of age in the context of longer standing selective mutism, aggression, and mild motor delays. His genetic evaluation included chromosomal microarray analysis and whole-exome sequencing. Sequencing revealed a previously unreported heterozygous de novo mutation c.385G>A in ATP1A3, predicted to result in a p.V129M amino acid change. This gene codes for a neuron-specific isoform of the catalytic α-subunit of the ATP-dependent transmembrane sodium–potassium pump. Heterozygous mutations in this gene have been reported as causing both sporadic and inherited forms of alternating hemiplegia of childhood and rapid-onset dystonia parkinsonism. We discuss the literature on phenotypes associated with known variants in ATP1A3, examine past functional studies of the role of ATP1A3 in neuronal function, and describe a novel clinical presentation associated with mutation of this gene.

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  title={A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia},
  author={Smedemark-Margulies, Niklas and Brownstein, Catherine A and Vargas, Sigella and Tembulkar, Sahil K and Towne, Meghan C and Shi, Jiahai and Gonzalez-Cuevas, Elisa and Liu, Kevin X and Bilguvar, Kaya and Kleiman, Robin J and others},
  journal={Molecular Case Studies},
  publisher={Cold Spring Harbor Laboratory Press}