Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome
C Dodé, J Levilliers, JM Dupont, A De Paepe… - Nature …, 2003 - nature.com
C Dodé, J Levilliers, JM Dupont, A De Paepe, N Le Dû, N Soussi-Yanicostas, RS Coimbra…
Nature genetics, 2003•nature.comWe 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 …
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 …
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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