In vitro effects of the mutations on cAMP production and TSH binding were investigated in COS7 cells. cAMP production was evaluated by transfecting a cAMP response element (CRE)-luciferase reporter with pSVL-TSHR and pSVK3-GNAS vectors.
A genetic and functional GNAS study was undertaken in a boy with morbid obesity (body mass index Z-score of 5 at the age of 3 yr, with a body fat fraction of 40%, which is more than twice normal), TSH resistance, pseudohypoparathyroidism, and a prothrombotic state.