Obesity-Associated <i>GNAS</i> Mutations and the Melanocortin Pathway

Abstract

Because pathogenic mutations may manifest with obesity alone, screening of children with severe obesity for <i>GNAS</i> deficiency may allow early diagnosis, improving clinical outcomes, and melanocortin agonists may aid in weight loss. <i>GNAS</i> mutations that are identified by means of unbiased genetic testing differentially affect GPCR signaling pathways that contribute to clinical heterogeneity. Monogenic diseases are clinically more variable than their classic descriptions suggest. (Funded by Wellcome and others.).