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

Autor:	Henriette A. Delemarre-van de Waal, Christine Petit, Marc Delpech, Philippe Bouchard, Françoise Baverel, Sylvie Compain-Nouaille, Marie-Laure Kottler, Christophe Pêcheux, Stefan Vermeulen, Nadia Soussi-Yanicostas, Dominique Le Tessier, Frank Speleman, Franco Sánchez-Franco, Roney S. Coimbra, Robert Saura, Sedigheh Delmaghani, Anne De Paepe, Yvan Bachelot, Jean-Claude Carel, Andrea Amalfitano, Catherine Dodé, Jean-Pierre Hardelin, Barbara Goulet-Salmon, Jacqueline Levilliers, Sylvie Cabrol, Jean-Michel Dupont, Jacques Young, Nathalie Le Dû, Corinne Cruaud, Odile Richard
Rok vydání:	2003
Předmět:	Genetics Isolated hypogonadotropic hypogonadism Mutation medicine.medical_specialty biology Kallmann syndrome Fibroblast growth factor receptor 1 KAL1 gene medicine.disease_cause medicine.disease X-inactivation Anosmin-1 Endocrinology Internal medicine biology.protein medicine Loss function
Zdroj:	Nature Genetics. 33:463-465
ISSN:	1546-1718 1061-4036
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::2b8fe9bd675767bdbaeee8422a0c5acd https://doi.org/10.1038/ng1122 Zobrazit plný text záznamu