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Yu L, Arbez N, Nucifora LG, Sell GL, Delisi LE, Ross CA, Margolis RL, Nucifora FC. A mutation in NPAS3 segregates with mental illness in a small family. Mol Psychiatry . 2013 Jan 22 ; PubMed Abstract

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Comment by:  Ben Pickard
Submitted 5 February 2013 Posted 5 February 2013

The paper by Yu et al. places another tick next to the NPAS3 candidate gene. Since the discovery of its disruption by a chromosomal translocation in a mother and daughter—both diagnosed with schizophrenia—it has cropped up several times in case-control association and mutation screens. This transcription factor has also accrued a catalogue of functional characteristics that align it well with potential schizophrenia pathologies. These include behavioral, neurodevelopmental, metabolic, and hippocampal neurogenesis deficits detected in a mouse knockout model, and a cellular pathology that includes mitochondrial fragility (Pickard et al., 2006; Sha et al., 2012; Pieper et al., 2010).

This latest chapter in the NPAS3 story details how the authors carried out resequencing in families densely affected with schizophrenia diagnoses. They identified a missense mutation (rs146677388) that changed the valine residue normally at this...  Read more

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