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Cold Spring Harb Mol Case Stud. 2016 Sep;2(5):a001008. doi: 10.1101/mcs.a001008.

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

Author information

1
Division of Immunology, Harvard Medical School, Boston, Massachusetts 02115, USA;; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA;
2
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA;; Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts 02115, USA;; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA;
3
Developmental Neuropsychiatry Research Program, Department of Psychiatry, Boston Children's Hospital, Boston, Massachusetts 02115, USA;
4
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA;; Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts 02115, USA;
5
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China;
6
Department of Genetics, Yale Center for Genome Analysis, Yale School of Medicine, New Haven, Connecticut 06511, USA;
7
Translational Neuroscience Center, Boston Children's Hospital, Boston, Massachusetts 02115, USA;; Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA;; Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts 02115, USA;
8
Division of Pediatric Neurology, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts 02118, USA;
9
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA;; Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts 02115, USA;; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA;; Division of Newborn Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA;
10
Developmental Neuropsychiatry Research Program, Department of Psychiatry, Boston Children's Hospital, Boston, Massachusetts 02115, USA;; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

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.

KEYWORDS:

psychotic mentation

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