title: Identification of mutations in the NUCB2/nesfatin gene in children with severe obesity.
abstract: Nesfatin-1 is the N-terminal fragment of nucleobindin-2 (NUCB2) that was identified as a novel satiety molecule in rodents. The protein is reported to exert anorexigenic effects and appears to play an important role in hypothalamic pathways regulating energy homeostasis and food intake. In this study, we hypothesized that mutations in the nesfatin encoding gene NUCB2 might cause obesity in humans. Therefore, we screened the entire coding region of the NUCB2 gene for mutations in a population of 471 obese children and adolescents. Mutation analysis of NUCB2 identified a total of seven sequence variants of which four were previously reported as polymorphisms. The remaining three variants included ex9+6G>C, L125H and K178X and were found in 3 unrelated individuals in the obese population only (0.6%). Biochemical experiments including ELISA and western blot were performed on plasma samples of the obese patient carrying the nonsense mutation K178X. However, neither NUCB2/nesfatin-1 immunoreactive plasma levels of the patient, nor expression of full length NUCB2 differed significantly from matched obese control individuals. In conclusion, we have identified the first genetic variants in the NUCB2 gene in obese individuals, although further functional characterization will be essential to verify disease causality of the mutations.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Universiteitsplein 1-2610 Antwerp, Belgium. doreen.zegers@ua.ac.be
authors.forename: Doreen
authors.initials: D
authors.lastname: Zegers
authors.forename: Sigri
authors.initials: S
authors.lastname: Beckers
authors.forename: Fenna
authors.initials: F
authors.lastname: de Freitas
authors.forename: Karen
authors.initials: K
authors.lastname: Jennes
authors.forename: Jasmijn K
authors.initials: JK
authors.lastname: Van Camp
authors.forename: Ilse L
authors.initials: IL
authors.lastname: Mertens
authors.forename: Kim
authors.initials: K
authors.lastname: Van Hoorenbeeck
authors.forename: Raoul P
authors.initials: RP
authors.lastname: Rooman
authors.forename: Kristine N
authors.initials: KN
authors.lastname: Desager
authors.forename: Guy
authors.initials: G
authors.lastname: Massa
authors.forename: Luc F
authors.initials: LF
authors.lastname: Van Gaal
authors.forename: Wim
authors.initials: W
authors.lastname: Van Hul
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D023061:Gene Order; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D000080866:Nucleobindins; D009765:Obesity / Q000235:genetics* / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins