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Nat Genet. 2017 Aug;49(8):1251-1254. doi: 10.1038/ng.3894. Epub 2017 Jun 19.

Truncating mutations in RBM12 are associated with psychosis.

Author information

1
deCODE Genetics/Amgen, Reykjavik, Iceland.
2
National Institute for Health and Welfare (THL), Helsinki, Finland.
3
Department of Psychiatry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
4
Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
5
Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
6
Department of Psychiatry, Landspitali, National University Hospital, Reykjavik, Iceland.
7
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
8
National Center of Addiction Medicine, Vogur Hospital, Reykjavik, Iceland.

Abstract

Thus far, a handful of highly penetrant mutations conferring risk of psychosis have been discovered. Here we used whole-genome sequencing and long-range phasing to investigate an Icelandic kindred containing ten individuals with psychosis (schizophrenia, schizoaffective disorder or psychotic bipolar disorder). We found that all affected individuals carry RBM12 (RNA-binding-motif protein 12) c.2377G>T (P = 2.2 × 10-4), a nonsense mutation that results in the production of a truncated protein lacking a predicted RNA-recognition motif. We replicated the association in a Finnish family in which a second RBM12 truncating mutation (c.2532delT) segregates with psychosis (P = 0.020). c.2377G>T is not fully penetrant for psychosis; however, we found that carriers unaffected by psychosis resemble patients with schizophrenia in their non-psychotic psychiatric disorder and neuropsychological test profile (P = 0.0043) as well as in their life outcomes (including an increased chance of receiving disability benefits, P = 0.011). As RBM12 has not previously been linked to psychosis, this work provides new insight into psychiatric disease.

PMID:
28628109
DOI:
10.1038/ng.3894
[Indexed for MEDLINE]

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