1. ¹Division of Molecular Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany
2. ²Department of Cell Biology, Paris-Lodron University Salzburg, Salzburg, Austria
3. ³Department of Child and Adolescent Psychiatry, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany

Correspondence: Professor A Poustka, Division of Molecular Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. E-mail: a.poustka@dkfz.de

⁴Current address: Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.

Received 19 May 2006; Revised 19 July 2006; Accepted 24 July 2006; Published online 29 August 2006.

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.