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A novel frameshift mutation in UPF3B identified in brothers affected with childhood onset schizophrenia and autism spectrum disorders

Molecular Psychiatry volume 16, pages 238–239 (2011)Cite this article

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A Corrigendum to this article was published on 07 September 2010

Childhood onset schizophrenia (COS) is a rare, severe form of schizophrenia for which definitive genetic causes remain elusive.1, 2 In this study, we report a novel 4-nucleotide deletion in the UPF3B gene, predicted to create a truncated protein, transmitted from a healthy mother to two affected brothers: one with comorbid diagnoses of COS, pervasive developmental disorder not otherwise specified and attention deficit hyperactivity disorder (ADHD), and the other with autism and ADHD. This work provides evidence that UPF3B, already described as a cause of syndromic and nonsyndromic X-linked mental retardation with or without autism,3, 4 is also involved in COS, autism spectrum disorders and ADHD.

Given that the asymptomatic mother was a carrier of the p.Q228fsX18 mutation identified in this study, we determined her X Chromosome Inactivation profile with the Human Androgen Receptor Gene (HUMARA) assay as described previously,6 using 200 ng of genomic DNA from peripheral blood. Only 24% of mother's blood cells expressed the X chromosome harboring the mutation, indicating that the mother showed a moderately skewed X inactivation pattern with a preferential inactivation (76:24) of the mutated X chromosome allele.

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References

  1. Rapoport JL, Addington AM, Frangou S . Mol Psychiatry 2005; 10: 434–449.

    Article  CAS  Google Scholar 

  2. Addington AM, Rapoport JL . Curr Psychiatry Rep 2009; 11: 156–161.

    Article  Google Scholar 

  3. Laumonnier F, Shoubridge C, Antar C, Nguyen LS, Van Esch H, Kleefstra T et al. Mol Psychiatry 2009; e-pub ahead of print 24 February 2009.

  4. Tarpey PS, Raymond FL, Nguyen LS, Rodriguez J, Hackett A, Vandeleur L et al. Nat Genet 2007; 39: 1127–1133.

    Article  CAS  Google Scholar 

  5. Gauthier J, Spiegelman D, Piton A, Lafreniere RG, Laurent S, St-Onge J et al. Am J Med Genet B Neuropsychiatr Genet 2009; 150B: 421–424.

    Article  CAS  Google Scholar 

  6. Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW . Am J Hum Genet 1992; 51: 1229–1239.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Berument SK, Rutter M, Lord C, Pickles A, Bailey A . Br J Psychiatry 1999; 175: 444–451.

    Article  CAS  Google Scholar 

  8. Rapoport J, Chavez A, Greenstein D, Addington A, Gogtay N . J Am Acad Child Adolesc Psychiatry 2009; 48: 10–18.

    Article  Google Scholar 

  9. Itsara A, Cooper GM, Baker C, Girirajan S, Li J, Absher D et al. Am J Hum Genet 2009; 84: 148–161.

    Article  CAS  Google Scholar 

  10. Mefford HC, Sharp AJ, Baker C, Itsara A, Jiang Z, Buysse K et al. N Engl J Med 2008; 359: 1685–1699.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD, USA

    A M Addington, N Gogtay, R Miller, J Tossell, J Bakalar, G Germain, P Gochman, R Long & J L Rapoport

  2. Centre of Excellence in Neuromics of Université de Montréal, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada

    J Gauthier, A Piton, A Raymond & G A Rouleau

  3. Department of Medicine, Université of Montréal, Montréal, QC, Canada

    J Gauthier, A Piton, A Raymond & G A Rouleau

  4. Centre of Excellence in Neuromics of Université de Montréal, CHU Sainte-Justine Research Center, Montréal, QC, Canada

    F F Hamdan

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  1. A M Addington
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  2. J Gauthier
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Correspondence to A M Addington.

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Addington, A., Gauthier, J., Piton, A. et al. A novel frameshift mutation in UPF3B identified in brothers affected with childhood onset schizophrenia and autism spectrum disorders. Mol Psychiatry 16, 238–239 (2011). https://doi.org/10.1038/mp.2010.59

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