A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia

Smedemark-Margulies, NiklasBrownstein, CatherineVargas, SigellaTembulkar, Sahil K.Towne, Meghan C.Shi, JiahaiGonzalez-Cuevas, ElisaLiu, Kevin X.Bilguvar, KayaKleiman, Robin J.Han, Min-JoonTorres, AlcyBerry, Gerard T.Yu, Timothy W.Beggs, AlanAgrawal, PankajGonzalez-Heydrich, Joseph2016-11-182016Smedemark-Margulies, N., C. A. Brownstein, S. Vargas, S. K. Tembulkar, M. C. Towne, J. Shi, E. Gonzalez-Cuevas, et al. 2016. “A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia.” Cold Spring Harbor Molecular Case Studies 2 (5): a001008. doi:10.1101/mcs.a001008. http://dx.doi.org/10.1101/mcs.a001008.2373-2865http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407579We 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.en-USpsychotic mentationA novel de novo mutation in ATP1A3 and childhood-onset schizophreniaJournal Article2016-11-1810.1101/mcs.a001008