title: Identification of the first deletion in the LRP5 gene in a patient with autosomal dominant osteopetrosis type I.
abstract: 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.
authors: Institute of Genetic and Biomedical Research-Milan Section, National Research Council, 20138 Milan, Italy. alessandra.pangrazio@itb.cnr.it
authors: Alessandra
authors: A
authors: Pangrazio
authors: Eveline
authors: E
authors: Boudin
authors: Elke
authors: E
authors: Piters
authors: Giuseppe
authors: G
authors: Damante
authors: Nadia
authors: N
authors: Lo Iacono
authors: Angela Valentina
authors: AV
authors: D'Elia
authors: Paolo
authors: P
authors: Vezzoni
authors: Wim
authors: W
authors: Van Hul
authors: Anna
authors: A
authors: Villa
authors: Cristina
authors: C
authors: Sobacchi
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