Deletion of codons 88-92 of the melanocortin-4 receptor gene: a novel deleterious mutation in an obese female. J Clin Endocrinol Metab 2003 Dec;88(12):5841-5
Date
12/13/2003Pubmed ID
14671178DOI
10.1210/jc.2003-030903Scopus ID
2-s2.0-0347993151 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
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.
Author List
Donohoue PA, Tao YX, Collins M, Yeo GS, O'Rahilly S, Segaloff DLMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Amino Acid Sequence
Base Sequence
Binding, Competitive
Cell Line
Codon
Cyclic AMP
Female
Gene Deletion
Humans
Ligands
Male
Middle Aged
Mutation
Obesity
Receptor, Melanocortin, Type 4