Sequencing of an additional 290 children with severe early-onset obesity with detectable leptin levels from the Genetics of Obesity Study (GOOS) did not reveal additional mutations in LEP. Because this cohort included patients from consanguineous families and with clinical features strongly suggestive of the disorder, these findings suggest that mutations resulting in a bioinactive form of leptin are a very rare cause of severe, early-onset obesity. Here, LEP is linked to obesity disorder.