title: Deletion of codons 88-92 of the melanocortin-4 receptor gene: a novel deleterious mutation in an obese female.
abstract: Genetic and pharmacological studies have shown that the melanocortin-4 receptor (MC4R) is an important regulator of food intake and energy homeostasis. Consistent with these studies, several mutations of the MC4R gene have been identified as being associated with early-onset severe obesity. We report here the first in-frame deletion mutation of the MC4R gene (delta88-92) in an obese female patient with onset of obesity at less than 5 yr of age. Functional analysis revealed that the mutant receptor is expressed well on the cell surface but completely devoid of ligand binding and cAMP generation in response to agonist stimulation. We conclude that this novel mutation is the cause of obesity of this patient.
authors.affiliation: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. patricia-donohoue@uiowa.edu
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Donohoue
authors.forename: Ya-Xiong
authors.initials: YX
authors.lastname: Tao
authors.forename: Malia
authors.initials: M
authors.lastname: Collins
authors.forename: Giles S H
authors.initials: GS
authors.lastname: Yeo
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Segaloff
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D001667:Binding, Competitive; D002460:Cell Line; D003062:Codon / Q000235:genetics*; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism
chemical_list: D003062:Codon; D008024:Ligands; D044105:Receptor, Melanocortin, Type 4; D000242:Cyclic AMP