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- Title
Kallmann syndrome: fibroblast growth factor signaling insufficiency?
- Authors
Dodé, Catherine; Hardelin, Jean-Pierre
- Abstract
Kallmann syndrome (KAL) is a developmental disease that combines hypogonadotropic hypogonadism and anosmia. Anosmia is related to the absence or hypoplasia of the olfactory bulbs. Hypogonadism is due to GnRH deficiency and is likely to result from the failed embryonic migration of GnRH-synthesizing neurons. These cells normally migrate from the olfactory epithelium to the forebrain along the olfactory nerve pathway. KAL is phenotypically and genetically heterogeneous. The gene responsible for the X-chromosome linked form of the disease (KAL1) has been identified in 1991.KAL1encodes anosmin-1, an approx. 95-kDa glycoprotein of unknown function which is present locally in various extracellular matrices during the period of organogenesis. The recent finding thatFGFR1mutations are involved in an autosomal dominant form of Kallmann syndrome (KAL2), combined with the analysis of mutant mouse embryos that no longer expressFgfr1in the telencephalon, suggests that the disease results from a deficiency in FGF signaling at the earliest stage of olfactory bulb morphogenesis. We propose that the role of anosmin-1 is to enhance FGF signaling and suggest that the gender difference in anosmin-1 dose (becauseKAL1partially escapes X-inactivation) explains the higher prevalence of the disease in males.
- Subjects
BRAIN diseases; HYPOGONADISM; NEURONS; OLFACTORY nerve; X chromosome; GLYCOPROTEINS
- Publication
Journal of Molecular Medicine, 2004, Vol 82, Issue 11, p725
- ISSN
0946-2716
- Publication type
Article
- DOI
10.1007/s00109-004-0571-y