2. Academic Validation
  3. Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome

Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome

  • Nat Genet. 2003 Apr;33(4):463-5. doi: 10.1038/ng1122.
Catherine Dodé 1,  Jacqueline Levilliers,  Jean-Michel Dupont,  Anne De Paepe,  Nathalie Le Dû,  Nadia Soussi-Yanicostas,  Roney S Coimbra,  Sedigheh Delmaghani,  Sylvie Compain-Nouaille,  Françoise Baverel,  Christophe Pêcheux,  Dominique Le Tessier,  Corinne Cruaud,  Marc Delpech,  Frank Speleman,  Stefan Vermeulen,  Andrea Amalfitano,  Yvan Bachelot,  Philippe Bouchard,  Sylvie Cabrol,  Jean-Claude Carel,  Henriette Delemarre-van de Waal,  Barbara Goulet-Salmon,  Marie-Laure Kottler,  Odile Richard,  Franco Sanchez-Franco,  Robert Saura,  Jacques Young,  Christine Petit,  Jean-Pierre Hardelin
Affiliations

Affiliation

  • 1 Institut Cochin et Laboratoire de Biochimie et Génétique Moléculaire, Hôpital Cochin, 75014 Paris, France.
PMID: 12627230 DOI: 10.1038/ng1122
Abstract

We took advantage of overlapping interstitial deletions at chromosome 8p11-p12 in two individuals with contiguous gene syndromes and defined an interval of roughly 540 kb associated with a dominant form of Kallmann syndrome, KAL2. We establish here that loss-of-function mutations in FGFR1 underlie KAL2 whereas a gain-of-function mutation in FGFR1 has been shown to cause a form of craniosynostosis. Moreover, we suggest that the KAL1 gene product, the extracellular matrix protein anosmin-1, is involved in FGF signaling and propose that the gender difference in anosmin-1 dosage (because KAL1 partially escapes X inactivation) explains the higher prevalence of the disease in males.

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