Title
Identification of the first deletion in the **LRP5** gene in a patient with Autosomal Dominant Osteopetrosis type I Identification of the first deletion in the **LRP5** gene in a patient with Autosomal Dominant Osteopetrosis type I
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
New York ,
Subject
Biology
Human medicine
Source (journal)
Bone / International Bone and Mineral Society. - New York
Volume/pages
49(2011) :3 , p. 568-571
ISSN
8756-3282
ISI
000293805100032
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/a07de3/022d5637.pdf
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