Deletion of Codons 88–92 of the Melanocortin-4 Receptor Gene: A Novel Deleterious Mutation in an Obese Female

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 repor...

Full description

Saved in:
Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2003-12, Vol.88 (12), p.5841-5845
Main Authors: Donohoue, Patricia A., Tao, Ya-Xiong, Collins, Malia, Yeo, Giles S. H., O’Rahilly, Stephen, Segaloff, Deborah L.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Amino Acid Sequence - genetics
Base Sequence - genetics
Binding, Competitive
Biological and medical sciences
Cell Line
Codon - genetics
Cyclic AMP - biosynthesis
Female
Gene Deletion
Hormones. Endocrine system
Humans
Ligands
Male
Medical sciences
Metabolic diseases
Middle Aged
Mutation
Obesity
Obesity - genetics
Pharmacology. Drug treatments
Receptor, Melanocortin, Type 4 - agonists
Receptor, Melanocortin, Type 4 - genetics
Receptor, Melanocortin, Type 4 - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 (Δ88–92) 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.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2003-030903