title: Monogenic obesity in humans.
abstract: Until relatively recently, the small number of identifiable inherited human diseases associated with marked obesity were complex, pleiotropic developmental disorders, the molecular basis for which were entirely obscure. The molecular basis for many of these complex syndromes, such as Bardet Beidl syndrome, has been revealed, providing novel insights into processes essential for human hypothalamic function and energy balance. In addition to these discoveries, which were the fruits of positional cloning, the molecular constituents of the signaling pathways responsible for the control of mammalian energy homeostasis have been identified, largely through the study of natural or artificial mutations in mice. We discuss the increasing number of human disorders that result from genetic disruption of the leptin-melanocortin pathways that have been identified. Practical implications of these findings for genetic counseling, prognostication, and even therapy have already emerged.
authors.affiliation: Departments of Medicine and Clinical Biochemistry, Cambridge University, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
authors.forename: I Sadaf
authors.initials: IS
authors.lastname: Farooqi
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
mesh_terms: D000293:Adolescent; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000235:genetics* / Q000628:therapy; D004734:Energy Metabolism / Q000235:genetics; D005817:Genetic Counseling; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D020738:Leptin / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics* / Q000628:therapy; D009767:Obesity, Morbid / Q000235:genetics* / Q000628:therapy; D010641:Phenotype; D011379:Prognosis; D044105:Receptor, Melanocortin, Type 4 / Q000172:deficiency; D015398:Signal Transduction / Q000235:genetics; D013577:Syndrome
chemical_list: D020738:Leptin; C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4