title: Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome.
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.
authors.affiliation: Institut Cochin et Laboratoire de Biochimie et Génétique Moléculaire, Hôpital Cochin, 75014 Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dodé
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Levilliers
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dupont
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.forename: Nathalie
authors.initials: N
authors.lastname: Le Dû
authors.forename: Nadia
authors.initials: N
authors.lastname: Soussi-Yanicostas
authors.forename: Roney S
authors.initials: RS
authors.lastname: Coimbra
authors.forename: Sedigheh
authors.initials: S
authors.lastname: Delmaghani
authors.forename: Sylvie
authors.initials: S
authors.lastname: Compain-Nouaille
authors.forename: Françoise
authors.initials: F
authors.lastname: Baverel
authors.forename: Christophe
authors.initials: C
authors.lastname: Pêcheux
authors.forename: Dominique
authors.initials: D
authors.lastname: Le Tessier
authors.forename: Corinne
authors.initials: C
authors.lastname: Cruaud
authors.forename: Marc
authors.initials: M
authors.lastname: Delpech
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.forename: Stefan
authors.initials: S
authors.lastname: Vermeulen
authors.forename: Andrea
authors.initials: A
authors.lastname: Amalfitano
authors.forename: Yvan
authors.initials: Y
authors.lastname: Bachelot
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouchard
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cabrol
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Carel
authors.forename: Henriette
authors.initials: H
authors.lastname: Delemarre-van de Waal
authors.forename: Barbara
authors.initials: B
authors.lastname: Goulet-Salmon
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Kottler
authors.forename: Odile
authors.initials: O
authors.lastname: Richard
authors.forename: Franco
authors.initials: F
authors.lastname: Sanchez-Franco
authors.forename: Robert
authors.initials: R
authors.lastname: Saura
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hardelin
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8; D041321:Chromosomes, Human, X; D005091:Exons; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007438:Introns; D017436:Kallmann Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D012737:Sex Factors; D015398:Signal Transduction
chemical_list: C076266:ANOS1 protein, human; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1