Group Number Female: Male Age (y) BMI (kg/m2) PWS 18 8: 10 24.6±5.0 33.9±9.0 Obese controlsa 14 10: 4 41.4±7.7 36.1±3.4 Lean controlsb 16 9: 7 42.8±11.0 25.1±3.5 LepR mutantsc 2 2: 0 16.0±4.2 68.6±4.2 LepR controlsd 7 4: 3 27.0±15.6 27.4±5.6 Mc4r mutantse 19 10: 9 29.8±15.7 34.8±10.3 Mc4r controlsf 22 15: 7 33.9±15.0 31.8±12.0 a, BMI= 30 kg/m2, genetically uncharacterized obesity. b, BMI< 30 kg/m2. c, Exon/intron 16 G/A substitution; truncated receptor lacks transmembrane and intracellular domains (ref. 2). d, First-degree relatives of subjects with LepR mutations (5 heterozygotes and 2 wild type). e, Each subject has one of the following heterozygous Mc4r mutations (refs. 3, 13 and data not shown): InsG47-48 frameshift (inactivates), Ile102Ser (inactivates), Ser295Pro (partially inactivates), Ile170Val (inactivates), Val50Met (partially inactivates), Ile251Leu (polymorphism), Ser58Cys (inactivates), Ala154Asp (partially inactivates), Val103Ile (polymorphism) or Leu250Gln (constitutively activates in vitro, but associated with obesity). f, Unaffected first-degree relatives of all but 4 Mc4r mutants, for whom no family controls were available. For these 4, unrelated controls matched for age, sex and BMI were used. Values shown are mean±sd