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Bone Abstracts (2013) 1 PP268 | DOI: 10.1530/boneabs.1.PP268

ECTS2013 Poster Presentations Genetics (17 abstracts)

No mutations in the serotonin related TPH1 and HTR1B genes in patients with monogenic sclerosing bone disorders

Eveline Boudin 1 , Karen Jennes 1 , Fenna de Freitas 1 , David Tegay 2 , Geert Mortier 1 & Wim Van Hul 1

1Department of Medical Genetics, Univeristy Hospital of Antwerp, Edegem, Belgium; 2Department of Medicine, New York Institute of Technology College of Osteopathic Medicine (NYITCOM), Old Westbury, New York, USA.

Since the identification of LRP5 as the causative gene for the osteoporosis pseudoglioma syndrome (OPPG) as well as the high bone mass (HBM) phenotype, LRP5 and the Wnt/β-catenin signalling have been extensively studied for their role in the differentiation and proliferation of osteoblasts, in the apoptosis of osteoblasts and osteocytes and in the response of bone to mechanical loading. However, more recently the direct effect of LRP5 on osteoblasts and bone formation has been questioned. Gene expression studies showed that mice lacking lrp5 have increased expression of tph1, the rate limiting enzyme for the production of serotonin in the gut. Furthermore mice lacking either tph1 or htr1B, the receptor for serotonin on the osteoblasts, were reported to have an increased bone mass due to increased bone formation. This led to the still controversial hypothesis that LRP5 influences bone formation indirectly by regulating the expression of thp1 and as a consequence influencing the production of serotonin in the gut. Based on these data we decided to evaluate the role of TPH1 and HTR1B in the development of craniotubular hyperostoses, a group of monogenic sclerosing bone dysplasias. Using Sanger sequencing, we screened the coding regions of both selected genes in 53 patients with a form of craniotubular hyperostosis which lack a mutation in the known causative genes LRP5, LRP4, and SOST. We found several common and rare coding variants in both studied genes. However, we could not identify disease-causing variants in neither of the tested genes and therefore, we cannot provide support for an important function of serotonin in the pathogenesis of sclerosing bone dysplasias.

Volume 1

European Calcified Tissue Society Congress 2013

Lisbon, Portugal
18 May 2013 - 22 May 2013

European Calcified Tissue Society 

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