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Nat Genet. 2003 Apr;33(4):440-2.
Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome.
Dodé C,
Levilliers J,
Dupont JM,
De Paepe A,
Le Dû N,
Soussi-Yanicostas N,
Coimbra RS,
Delmaghani S,
Compain-Nouaille S,
Baverel F,
Pêcheux C,
Le Tessier D,
Cruaud C,
Delpech M,
Speleman F,
Vermeulen S,
Amalfitano A,
Bachelot Y,
Bouchard P,
Cabrol S,
Carel JC,
Delemarre-van de Waal H,
Goulet-Salmon B,
Kottler ML,
Richard O,
Sanchez-Franco F,
Saura R,
Young J,
Petit C,
Hardelin JP.
Institut Cochin et Laboratoire de Biochimie et Génétique Moléculaire, Hôpital Cochin, 75014 Paris, France.
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.
PMID: 12627230 [PubMed - indexed for MEDLINE]