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A missense mutation in a novel gene encoding a putative cation channel is associated with catatonic schizophrenia in a large pedigree

Molecular Psychiatry volume 6, pages 302–306 (2001)Cite this article

Abstract

Schizophrenia is a common and etiologically heterogeneous disorder. Although inheritance of schizophrenic syndromes is complex with genetic and environmental factors contributing to the clinical phenotype, periodic catatonia, a familial subtype of catatonic schizophrenia, appears to be transmitted in an autosomal dominant manner. We report here that a Leu309Met mutation in WKL1, a positional candidate gene on chromosome 22q13.33 encoding a putative non-selective cation channel expressed exclusively in brain, co-segregates with periodic catatonia in an extended pedigree. Structural analyses revealed that this missense mutation results in conformational changes of the mutant protein. Our results not only underscore the importance of genetic mechanisms in the etiology of schizophrenic syndromes, but also provide a better understanding of the pathogenesis and incapacitating course of catatonic schizophrenia and related disorders.

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Acknowledgements

The authors would like to express their gratitude to the study participants and their family. They also thank P Riederer for sharing human brain samples, M Schartl and S Scherer for their help with the protein analysis, and C Müller-Reible for helpful discussions.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, D-97080, Germany

    J Meyer, A Huberth, G Ortega, Y V Syagailo, S Jatzke, R Mössner, I Ulzheimer-Teuber, G Stöber, A Schmitt & K P Lesch

  2. GSF – National Research Center for Environment and Health, Neuherberg, D-85764, Germany

    T M Strom

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  1. J Meyer
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  2. A Huberth
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  3. G Ortega
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  8. I Ulzheimer-Teuber
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Correspondence to J Meyer or K P Lesch.

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Meyer, J., Huberth, A., Ortega, G. et al. A missense mutation in a novel gene encoding a putative cation channel is associated with catatonic schizophrenia in a large pedigree. Mol Psychiatry 6, 302–306 (2001). https://doi.org/10.1038/sj.mp.4000869

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  • DOI: https://doi.org/10.1038/sj.mp.4000869

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