Obesity-Associated GNAS Mutations and the Melanocortin Pathway

To the Editor: In an exome-sequencing study involving 2548 children who presented with severe obesity, Mendes de Oliveira et al. (Oct. 21 issue)(1) reported 19 different GNAS variants in 22 patients with severe childhood-onset obesity without features of pseudohypoparathyroidism. The majority of these variants (16 of 19) were missense variants that were functionally characterized for their effects on signaling by the G alpha(s) subunit-coupled melanocortin 4 receptor. The authors suggest that children with severe childhood-onset obesity should be screened for GNAS variants in accordance with the diagnostic approach favored by Mantovani et al.(2) to enable early diagnosis and treatment. However, interpreting . . .

Automated summary

In an exome-sequencing study, GNAS variants were found in children with severe childhood-onset obesity. These variants affect the signaling of the melanocortin 4 receptor. The authors suggest screening for GNAS variants in children to enable early diagnosis and treatment.