1. Mutation screening of the ubiquitin ligase gene RNF135 in French patients with autism
- Author
-
Patrick Vourc'h, Annick Toutain, Catherine Barthélémy, Joëlle Malvy, Loïc Decalonne, Hélène Bénédetti, Rose-Anne Thépault, Frédéric Laumonnier, Refaat Tabagh, Sylviane Marouillat, Frédérique Bonnet-Brilhault, Agathe Paubel, Christian R. Andres, Julie Tastet, University Medical Center [Utrecht], Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), INSERM 930, CHU Bretonneau, Université Francois Rabelais [Tours], Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau
- Subjects
Adult ,Male ,Adolescent ,[SDV]Life Sciences [q-bio] ,Ubiquitin-Protein Ligases ,Mutation, Missense ,Bioinformatics ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Ubiquitin ,Genotype ,Genetics ,medicine ,Humans ,Missense mutation ,Coding region ,RNA, Messenger ,Autistic Disorder ,Allele ,Child ,Gene ,Biological Psychiatry ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,biology ,Middle Aged ,medicine.disease ,3. Good health ,Ubiquitin ligase ,Psychiatry and Mental health ,Case-Control Studies ,Child, Preschool ,biology.protein ,Autism ,Female ,France ,Carrier Proteins ,030217 neurology & neurosurgery - Abstract
International audience; Many genes are now thought to confer susceptibility to autism. Despite the fact that this neuropsychiatric disease appears to be related to several different causes, common cellular and molecular pathways have emerged and point to synaptic dysfunction or cellular growth. Several studies have indicated the importance of the ubiquitin pathway in synaptic function and the aetiology of autism. Here, we focused on the ring finger protein 135 (RNF135) gene, encoding an E3 ubiquitin ligase expressed in the cortex and cerebellum, and located in the NF1 gene locus in 17q11.2, a region linked to autism. We carried out a genetic analysis of the coding sequence of RFN135 in a French cohort of patients with autism and observed a significantly increased frequency of genotypes carrying the rare allele of the rs111902263 (p.R115K) missense variant in patients (P=0.0019, odds ratio : 4.23, 95% confidence interval : 1.87-9.57). Particularly, three unrelated patients showed a homozygous genotype for K115, a situation not observed in the 1812 control individuals. Further cellular and molecular studies are required to elucidate the role of this gene and the variant K115 in brain development and neuronal function.
- Published
- 2015
- Full Text
- View/download PDF