title: Mutational analysis of the serotonin receptor 5HT2c in severe early-onset human obesity.
abstract: Deletion of the serotonin receptor 5HT2c in mice results in increased food intake and obesity. We screened 95 individuals with severe early-onset obesity for mutations in the coding sequence of this gene. We found a novel missense variant c.1255A > G (Thr419Ala) in a single Caucasian subject that was not found in 192 Caucasian control subjects. In transiently-transfected COS cells, the Thr419Ala variant was indistinguishable from the wild-type receptor in its ability to generate inositol phosphate, although differences in coupling to other pathways were not excluded. Three previously unreported silent variants: IVS3 + 30G > A, IVS3 + 80C > G and IVS4 - 31A > G were found with prevalences of 11.5%, 0.5% and 17.9%, respectively. In conclusion, mutations in 5HT2c are unlikely to be a common cause of severe early-onset human obesity. The identification of several novel polymorphisms at this locus may aid future genetic epidemiological studies.
authors.affiliation: Department of Clinical Biochemistry and Cambridge Institute for Medical Research, Addenbrooke's Hospital, UK.
authors.forename: William T
authors.initials: WT
authors.lastname: Gibson
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Ebersole
authors.forename: Sumit
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Peter
authors.initials: P
authors.lastname: Clayton
authors.forename: I Sadaf
authors.initials: IS
authors.lastname: Farooqi
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Sealfon
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D010375:Pedigree; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics* / Q000378:metabolism*
chemical_list: D044405:Receptor, Serotonin, 5-HT2C