Publication
Title
Identification of the first deletion in the **LRP5** gene in a patient with Autosomal Dominant Osteopetrosis type I
Author
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.
Language
English
Source (journal)
Bone / International Bone and Mineral Society. - New York
Publication
New York : 2011
ISSN
8756-3282
Volume/pages
49:3(2011), p. 568-571
ISI
000293805100032
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
[E?say:metaLocaldata.cgzprojectinf]
Targeting LRP5 to increase bone formation in osteoporosis (TALOS).
Genetic and functional analysis of two genes underlying an osteopetrotic rat model (incisors absent and osteopetrotic).
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 10.11.2011
Last edited 22.09.2017
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