Congenital leptin deficiency is associated with severe early-onset obesity in humans

Nature. 1997 Jun 26;387(6636):903-8. doi: 10.1038/43185.


The extreme obesity of the obese (ob/ob) mouse is attributable to mutations in the gene encoding leptin, an adipocyte-specific secreted protein which has profound effects on appetite and energy expenditure. We know of no equivalent evidence regarding leptin's role in the control of fat mass in humans. We have examined two severely obese children who are members of the same highly consanguineous pedigree. Their serum leptin levels were very low despite their markedly elevated fat mass and, in both, a homozygous frame-shift mutation involving the deletion of a single guanine nucleotide in codon 133 of the gene for leptin was found. The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Animals
  • Body Composition
  • CHO Cells
  • Child
  • Child, Preschool
  • Consanguinity
  • Cricetinae
  • Female
  • Frameshift Mutation
  • Homozygote
  • Humans
  • Leptin
  • Male
  • Metabolism, Inborn Errors / blood
  • Metabolism, Inborn Errors / genetics*
  • Mice
  • Mice, Obese
  • Molecular Sequence Data
  • Obesity / blood
  • Obesity / genetics*
  • Pedigree
  • Polymorphism, Single-Stranded Conformational
  • Proteins / genetics
  • Proteins / metabolism*
  • Sequence Analysis, DNA
  • Transfection


  • Leptin
  • Proteins

Associated data

  • GENBANK/U18915