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Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism

Molecular Psychiatry volume 11, pages 1073–1084 (2006)Cite this article

Abstract

Autism has a strong genetic background with a higher frequency of affected males suggesting involvement of X-linked genes and possibly also other factors causing the unbalanced sex ratio in the etiology of the disorder. We have identified two missense mutations in the ribosomal protein gene RPL10 located in Xq28 in two independent families with autism. We have obtained evidence that the amino-acid substitutions L206M and H213Q at the C-terminal end of RPL10 confer hypomorphism with respect to the regulation of the translation process while keeping the basic translation functions intact. This suggests the contribution of a novel, possibly modulating aberrant cellular function operative in autism. Previously, we detected high expression of RPL10 by RNA in situ hybridization in mouse hippocampus, a constituent of the brain limbic system known to be afflicted in autism. Based on these findings, we present a model for autistic disorder where a change in translational function is suggested to impact on those cognitive functions that are mediated through the limbic system.

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Acknowledgements

We thank all the families for their cooperation and the professionals for their support in collecting data; S Bölte for establishment of the patient database; U Ernst, H Bausbacher and A Irsigler for excellent technical assistance; K Oender, M Loeffler and T Karl for expert advice on cloning strategies; H Zhu and J Zhou for expert assistance in ribosomal profile analyses; S Bechtel for stimulating discussions; S Wiemann and D Arlt for critical reading of the manuscript. LBK wishes to thank M Breitenbach for continuous and generous support of her work. This work was supported by grants from the Deutsche Forschungsgemeinschaft to AP and FP and in part by grant 01GR0420 of the National Genome Research Network, funded by the Bundesministerium für Bildung und Forschung, Germany.

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Author notes

  1. A Kolb-Kokocinski

    Present address: Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK

Authors and Affiliations

  1. Division of Molecular Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany

    S M Klauck, B Felder, A Kolb-Kokocinski, C Schuster, I Schupp, R Wellenreuther & A Poustka

  2. Department of Cell Biology, Paris-Lodron University Salzburg, Salzburg, Austria

    A Chiocchetti & L Breitenbach-Koller

  3. Department of Child and Adolescent Psychiatry, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany

    G Schmötzer & F Poustka

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  1. S M Klauck
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Correspondence to A Poustka.

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Klauck, S., Felder, B., Kolb-Kokocinski, A. et al. Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism. Mol Psychiatry 11, 1073–1084 (2006). https://doi.org/10.1038/sj.mp.4001883

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