TY - JOUR
T1 - Identification of the first deletion in the LRP5 gene in a patient with Autosomal Dominant Osteopetrosis type I
AU - Pangrazio, Alessandra
AU - Boudin, Eveline
AU - Piters, Elke
AU - Damante, Giuseppe
AU - Iacono, Nadia Lo
AU - D'Elia, Angela Valentina
AU - Vezzoni, Paolo
AU - Van Hul, Wim
AU - Villa, Anna
AU - Sobacchi, Cristina
PY - 2011/9
Y1 - 2011/9
N2 - In the last decade, the low-density lipoprotein receptor-related protein 5 (LRP5) gene, coding for a coreceptor in the canonical Wnt signalling pathway, has been shown to play an important role in regulating bone mass and to be involved in the pathogenesis of several bone disorders. Here we describe a patient who presented with a clinical picture of Autosomal Dominant Osteopetrosis type I (ADO I), in whom we could identify the first deletion in the LRP5 gene causing increased bone mass. This mutation caused the in-frame deletion of two amino acids in the fourth blade of the first propeller of the protein, namely the highly conserved glycine at position 171 and the following glutamate residue. In vitro studies suggested that the pathogenic effect of this novel mutation could be due to a decreased inhibition of Wnt signalling by the antagonistic proteins sclerostin and Dickkopf-1, encoded respectively by the SOST and DKK1 genes, in the presence of mutated LRP5. Our results highlight an increasing molecular heterogeneity in LRP5-related bone diseases.
AB - In the last decade, the low-density lipoprotein receptor-related protein 5 (LRP5) gene, coding for a coreceptor in the canonical Wnt signalling pathway, has been shown to play an important role in regulating bone mass and to be involved in the pathogenesis of several bone disorders. Here we describe a patient who presented with a clinical picture of Autosomal Dominant Osteopetrosis type I (ADO I), in whom we could identify the first deletion in the LRP5 gene causing increased bone mass. This mutation caused the in-frame deletion of two amino acids in the fourth blade of the first propeller of the protein, namely the highly conserved glycine at position 171 and the following glutamate residue. In vitro studies suggested that the pathogenic effect of this novel mutation could be due to a decreased inhibition of Wnt signalling by the antagonistic proteins sclerostin and Dickkopf-1, encoded respectively by the SOST and DKK1 genes, in the presence of mutated LRP5. Our results highlight an increasing molecular heterogeneity in LRP5-related bone diseases.
KW - Bone
KW - LRP5
KW - Osteopetrosis
KW - Osteosclerosis
KW - Wnt signalling
UR - http://www.scopus.com/inward/record.url?scp=79960615546&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960615546&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2011.05.006
DO - 10.1016/j.bone.2011.05.006
M3 - Article
C2 - 21600326
AN - SCOPUS:79960615546
VL - 49
SP - 568
EP - 571
JO - Bone
JF - Bone
SN - 8756-3282
IS - 3
ER -