Melanocortin 4 Receptor Mutations in a Large Cohort of Severely Obese Adults: Prevalence, Functional Classification, Genotype-Phenotype Relationship, and Lack of Association with Binge Eating

Context: Heterozygous mutations in the melanocortin-4 receptor (MC4R) gene are the most common monogenic form of severe obesity in children. There are conflicting reports regarding the prevalence, nature, and pathogenic effects of MC4R mutations in adults with severe late-onset obesity. Objective: Our objective was to determine the prevalence of MC4R mutations in a cohort of severely obese adults and to determine the clinical phenotype and the phenotype-genotype relationship within adult MC4R mutation carriers. Design and Setting: We conducted an observational study at a referral center. Patients or Other Participants: Participants included 769 adult patients with body mass index of at least 35 kg/m2 and 444 nonobese control individuals. Interventions: There were no interventions. Main Outcome Measures: We assessed the prevalence of pathogenic MC4R mutations, functional characteristics of the detected mutations, phenotype, and phenotype-genotype relationship within mutation carriers. Results: The global p...