title: Mutation screening of the ubiquitin ligase gene RNF135 in French patients with autism.
abstract: 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.
authors.affiliation: aUMR INSERM U930, University François-Rabelais bCHRU Tours, Department of Pedopsychiatry cCHRU Tours, Department of Biochemistry and Molecular Biology dCNRS UPR 4301, CBM, Orléans.
authors.forename: Julie
authors.initials: J
authors.lastname: Tastet
authors.forename: Loïc
authors.initials: L
authors.lastname: Decalonne
authors.forename: Sylviane
authors.initials: S
authors.lastname: Marouillat
authors.forename: Joëlle
authors.initials: J
authors.lastname: Malvy
authors.forename: Rose-Anne
authors.initials: RA
authors.lastname: Thépault
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.forename: Agathe
authors.initials: A
authors.lastname: Paubel
authors.forename: Refaat
authors.initials: R
authors.lastname: Tabagh
authors.forename: Hélène
authors.initials: H
authors.lastname: Bénédetti
authors.forename: Frédéric
authors.initials: F
authors.lastname: Laumonnier
authors.forename: Catherine
authors.initials: C
authors.lastname: Barthélémy
authors.forename: Frédérique
authors.initials: F
authors.lastname: Bonnet-Brilhault
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
authors.forename: Patrick
authors.initials: P
authors.lastname: Vourc'h
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012333:RNA, Messenger / Q000235:genetics; D044767:Ubiquitin-Protein Ligases; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D012333:RNA, Messenger; C522809:RNF135 protein, human; D044767:Ubiquitin-Protein Ligases