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Evidence that a DISC1 frame-shift deletion associated with psychosis in a single family may not be a pathogenic mutation

Molecular Psychiatry volume 11, pages 798–799 (2006)Cite this article

Recently, Sachs et al.1 reported intra-familial association of a frame-shift mutation at the extreme 3′ end of exon 12 of the gene Disrupted in Schizophrenia 1 (DISC1) with schizophrenia and schizoaffective phenotypes. In our own sample, we identified this mutation in none of 655 schizophrenia cases but two of 694 non-psychiatrically screened controls. Our findings suggest that this mutation may not play a major role in influencing susceptibility to psychosis.

DISC1 is located on 1q42.1, a region implicated in linkage studies of schizophrenia, bipolar disorder and schizoaffective disorder.2, 3, 4, 5 This locus was originally implicated from the study of a Scottish family in which the balanced translocation t(1;11)(q42;q14.3) co-segregated with major mental disorders, the translocation disrupting a gene that was named DISC1.6 Association studies have also implicated DISC1.7, 8, 9, 10 Sachs et al.1 reported a frame-shift mutation at the extreme 3′ end of exon 12 of DISC1 that was identified in three siblings (two with schizophrenia, one with schizoaffective disorder) and their asymptomatic father, but not in 424 control individuals. The frame-shift is caused by a 4 bp deletion of one of two adjacent TCAT tetramers and leads to a truncated protein with nine abnormal amino acids at the C-terminus. To further investigate the potential pathogenic relevance of this mutation we genotyped a schizophrenia case–control sample comprising 1349 individuals.

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References

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Authors and Affiliations

  1. Department of Psychological Medicine, The Henry Wellcome Building for Biomedical Research in Wales, Cardiff University, School of Medicine, Heath Park, Cardiff, CF14 4XN, UK

    E K Green, N Norton, T Peirce, D Grozeva, G Kirov, M J Owen, M C O'Donovan & N Craddock

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  1. E K Green
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  2. N Norton
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  3. T Peirce
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  4. D Grozeva
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  5. G Kirov
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  6. M J Owen
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  7. M C O'Donovan
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  8. N Craddock
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Green, E., Norton, N., Peirce, T. et al. Evidence that a DISC1 frame-shift deletion associated with psychosis in a single family may not be a pathogenic mutation. Mol Psychiatry 11, 798–799 (2006). https://doi.org/10.1038/sj.mp.4001853

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  • DOI: https://doi.org/10.1038/sj.mp.4001853

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