Mechanisms of disease: Insights into X-linked and autosomal-dominant Kallmann syndrome.
Kallmann syndrome (KS) is a disorder characterized by hypogonadotropic hypogonadism and anosmia. Although KS is genetically heterogeneous, only two causal genes have been identified to date. These include an X-linked gene that encodes anosmin 1 and an autosomal gene that encodes fibroblast growth factor receptor 1. Mutations in these two genes result in disorders that often include, but are not limited to, severe defects in olfactory and reproductive functions. In this respect, KS can be regarded as a 'human model' for understanding critical factors that regulate olfactory and reproductive development. Here we give an overview of the disorders that stem from mutations in these two genes, with special emphasis on the cellular mechanisms underlying olfactory and reproductive anomalies. Other, less well-known aspects of KS, such as the convergence of symptoms in patients with different genetic forms of KS and the unpredictable manifestation of KS symptoms, are also discussed.
Tsai
Pei-San
PS
Department of Integrative Physiology, University of Colorado at Boulder, CO 80309-0354, USA. pei-san.tsai@colorado.edu
Gill
John C
JC
D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology; D050172:Genes, X-Linked; D006801:Humans; D017436:Kallmann Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000502:physiology
C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1