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Patricia A. Donohoue, Ya-Xiong Tao, Malia Collins, Giles S. H. Yeo, Stephen O’Rahilly, Deborah L. Segaloff, Deletion of Codons 88–92 of the Melanocortin-4 Receptor Gene: A Novel Deleterious Mutation in an Obese Female, The Journal of Clinical Endocrinology & Metabolism, Volume 88, Issue 12, 1 December 2003, Pages 5841–5845, https://doi.org/10.1210/jc.2003-030903
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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 (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.