title: Disorders of puberty: inactivating and activating molecular mutations.
abstract: Recent developments have increased our understanding of the molecular mechanisms that are responsible for several disorders of puberty. Specific gene mutations have been identified in three syndromes, one that is associated with delayed puberty (Kallmann syndrome) and two that are associated with precocious puberty (McCune-Albright syndrome and familial male precocious puberty). Mutations in the KAL gene have been shown to be responsible for cases of X-linked Kallmann syndrome. This gene encodes a protein that is believed to be involved in neural target recognition and protease inhibition. In McCune-Albright syndrome, heterozygous, postzygotic somatic mutations of the alpha-subunit of the stimulatory guanine nucleotide binding protein Gs have been shown to stimulate constitutive G protein activation and long-term cyclic adenosine monophosphate production. Similarly, familial male precocious puberty has been linked to gain-in-function mutations that result in increased levels of cyclic adenosine monophosphate; however, these mutations are found in the luteinizing hormone receptor gene itself. The clinical manifestations and the recent molecular advances in each of these three syndromes are explored.
authors.affiliation: Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis 46202, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: DiMeglio
authors.forename: O H
authors.initials: OH
authors.lastname: Pescovitz
mesh_terms: D000242:Cyclic AMP / Q000235:genetics; D016326:Extracellular Matrix Proteins; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics; D005796:Genes / Q000235:genetics; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D017436:Kallmann Syndrome / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D011480:Protease Inhibitors; D011628:Puberty, Delayed / Q000235:genetics*; D011629:Puberty, Precocious / Q000235:genetics*; D011974:Receptors, LH / Q000235:genetics; D014960:X Chromosome
chemical_list: C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D011480:Protease Inhibitors; D011974:Receptors, LH; D000242:Cyclic AMP; D019204:GTP-Binding Proteins