title: Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism.
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.
authors.affiliation: Division of Molecular Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: S M
authors.initials: SM
authors.lastname: Klauck
authors.forename: B
authors.initials: B
authors.lastname: Felder
authors.forename: A
authors.initials: A
authors.lastname: Kolb-Kokocinski
authors.forename: C
authors.initials: C
authors.lastname: Schuster
authors.forename: A
authors.initials: A
authors.lastname: Chiocchetti
authors.forename: I
authors.initials: I
authors.lastname: Schupp
authors.forename: R
authors.initials: R
authors.lastname: Wellenreuther
authors.forename: G
authors.initials: G
authors.lastname: Schmötzer
authors.forename: F
authors.initials: F
authors.lastname: Poustka
authors.forename: L
authors.initials: L
authors.lastname: Breitenbach-Koller
authors.forename: A
authors.initials: A
authors.lastname: Poustka
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D041321:Chromosomes, Human, X; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008959:Models, Neurological; D020125:Mutation, Missense; D010375:Pedigree; D014176:Protein Biosynthesis / Q000235:genetics*; D000080882:Ribosomal Protein L10; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C000630686:RPL10 protein, human; D012269:Ribosomal Proteins; C000630690:Rpl10 protein, mouse