Characterization of Rare Variants in MC4R in African American and Latino Children With Severe Early-Onset Obesity

Abstract Context Mutations in melanocortin receptor (MC4R) are the most common cause of monogenic obesity in children of European ancestry, but little is known about their prevalence in children from the minority populations in the United States. Objective This study aims to identify the prevalence of MC4R mutations in children with severe early-onset obesity of African American or Latino ancestry. Design and Setting Participants were recruited from the weight management clinics at two hospitals and from the institutional biobank at a third hospital. Sequencing of the MC4R gene was performed by whole exome or Sanger sequencing. Functional testing was performed to establish the surface expression of the receptor and cAMP response to its cognate ligand α-melanocyte–stimulating hormone. Participants Three hundred twelve children (1 to 18 years old, 50% girls) with body mass index (BMI) >120% of 95th percentile of Centers for Disease Control and Prevention 2000 growth charts at an age