Sclerosteosis

A rare, severe autosomal recessive sclerosing bone dysplasia characterized by progressive skeletal overgrowth (hyperostosis). Syndactyly is a variable manifestation. The majority of affected individuals have been reported in the Afrikaner population of South Africa. Mutations in the SOST gene have been identified. OMIM: 269500

Also Known As:

Networked: 42 relevant articles (1 outcomes, 4 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Osteoporosis
2.	Pycnodysostosis
3.	Osteopetrosis
4.	Bone Diseases (Bone Disease)
5.	Osteochondrodysplasias (Spondyloepiphyseal Dysplasia)

Experts

1.	Papapoulos, Socrates E: 6 articles (01/2017 - 06/2005)
2.	van Bezooijen, Rutger L: 4 articles (12/2011 - 06/2005)
3.	Hamersma, Herman: 3 articles (12/2011 - 11/2005)
4.	Appelman-Dijkstra, Natasha M: 2 articles (01/2017 - 06/2016)
5.	van Lierop, Antoon H: 2 articles (01/2017 - 12/2011)
6.	Van Hul, Wim: 2 articles (04/2016 - 12/2008)
7.	Boschert, Verena: 2 articles (04/2015 - 01/2013)
8.	Mueller, Thomas D: 2 articles (04/2015 - 01/2013)
9.	Loveridge, Nigel: 2 articles (12/2011 - 11/2005)
10.	Löwik, C W G M: 2 articles (08/2010 - 01/2005)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Sclerosteosis:

1.	Proteins (Proteins, Gene)FDA Link 02/01/2002 - "In a previous study, we positionally cloned a novel gene, called SOST, from the linkage interval and identified three different, homozygous mutations in the SOST gene in sclerosteosis patients leading to loss of function of the underlying protein. " 01/01/2016 - "The autosomal-recessive disease that later was named sclerosteosis was found to be caused by a mutation in the SOTS gene causing a lack of the protein sclerostin. " 03/01/2014 - "The SOST gene, which encodes the protein sclerostin, was identified through genetic linkage analysis of sclerosteosis and van Buchem's disease patients. " 08/01/2011 - "Patients with sclerosteosis lack the bone regulatory protein sclerostin, have excessive bone formation, and are typically above average in height. " 12/01/2008 - "The sclerosteosis gene has been mapped to chromosome 17q12-21 and is currently known as the SOST gene encoding the sclerostin protein. "
2.	AntibodiesIBA 01/01/2020 - "The discovery that sclerostin is the defective protein underlying the rare heritable bone mass disorder, sclerosteosis, ultimately led to development of anti-sclerostin antibodies as a new treatment for osteoporosis. "
3.	Nonsense Codon (Nonsense Mutation)IBA 02/01/2016 - "Sclerosteosis caused by a novel nonsense mutation of SOST in a consanguineous family." 03/01/2014 - "We report here a 30-years-old Moroccan man presented with typical clinical and radiological features of sclerosteosis who carries a novel homozygous mutation in the SOST gene, characterized as a nonsense mutation (c.79C > T; p.Gln27∗) in exon 1 of the SOST gene. " 12/01/2008 - "The radiological and clinical features are described, and the diagnosis of sclerosteosis was confirmed in both cases by mutation analysis of the SOST gene showing a homozygous nonsense mutation (Trp124X) in the two patients. " 03/01/2001 - "Two nonsense mutations and one splice site mutation were identified in sclerosteosis patients, but no mutations were found in a fourth sclerosteosis patient nor in the patients from the van Buchem family. "
4.	Messenger RNA (mRNA)IBA 09/01/2011 - "The mRNA and protein levels of sclerosteosis (Sost) and Dickkopf 1 (Dkk1), inhibitors of Wnt signaling, increased. " 07/04/2020 - "cultured MLO-Y4 osteocytes were exposed to different concentrations of titanium (Ti) particles, cell viability was measured using the Cell Counting Kit-8 (CCK-8) assay, apoptosis of MLO-Y4 cells was evaluated by flow cytometry, Real-time PCR quantification of mRNA expression of SOST, at the same time with Western Blot detection sclerosteosis protein expression levels.MC3T3-E1 cells culture with MLO-Y4 cells exposed to different concentrations of titanium (Ti) particles in vitro, in order to detection of osteoblast osteogenetic activity. " 07/01/2014 - "SI decreased sost mRNA and sclerosteosis protein expression in a dose-dependent manner, and increased β-catenin proteins expression in femur of OVX rats. " 05/01/2005 - "The cells were identified by morphology, cytochemical staining, immunocytochemical staining and mRNA expression of phosphate-regulating gene with homology to endopeptidases on the X chromosome (PHEX) and sclerosteosis/van Buchem disease gene (SOST). "
5.	Cystine (L-Cystine)IBA 10/01/2004 - "Sclerostin (SOST), a member of the cystine-knot superfamily, is essential for proper skeletogenesis because a loss-of-function mutation in the SOST gene results in sclerosteosis featured with massive bone growth in humans. " 01/01/2013 - "Based on a Sclerostin variant found in a Turkish family suffering from Sclerosteosis we generated a Sclerostin mutant with cysteines 84 and 142 exchanged thereby removing the third disulfide bond of the cystine-knot. " 04/01/2015 - "The secreted cystine-knot protein sclerostin was first identified from genetic screening of patients suffering from the rare bone-overgrowth diseases sclerosteosis and van Buchem disease. " 03/01/2001 - "Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein."
6.	Low Density Lipoprotein Receptor-Related Protein-5IBA 06/01/2007 - "The recent identification of a link between bone mass in humans and gain- or loss-of-function mutations in the Wnt coreceptor low-density lipoprotein receptor-related protein 5 (osteoporosis pseudoglioma syndrome, high bone mass trait) or in the Wnt antagonist sclerostin (sclerosteosis, van Buchem syndrome) has called the attention of academic and industry scientists and clinicians to the importance of this signaling pathway in skeletal biology and disease. " 10/01/2008 - "Finally, several of our specific-linkage areas encompass prominent candidate genes: type 1 collagen (COL1A1) and the sclerosteosis/van Buchem disease (SOST) genes on 17q21-23; the low-density lipoprotein receptor-related protein 5 (LRP5) gene on 11q12-13; and the rank ligand gene on 13q12-14. "
7.	LDL Receptors (LDL Receptor)IBA 03/17/2015 - "Lrp4 (low-density lipoprotein receptor related protein 4) is a member of the LDL receptor family, whose mutations have been identified in patients with high-bone-mass disorders, such as sclerosteosis and van Buchem diseases. " 01/01/2019 - "Low-density lipoprotein receptor-related protein 4 (LRP4) is a multi-functional protein implicated in bone, kidney and neurological diseases including Cenani-Lenz syndactyly (CLS), sclerosteosis, osteoporosis, congenital myasthenic syndrome and myasthenia gravis. "
8.	Glycoproteins (Glycoprotein)IBA 01/01/2018 - "Sclerosteosis is caused by loss-of-function mutations in the SOST gene which encodes a secreted glycoprotein, sclerostin. " 05/01/2021 - "The SOST gene, which encodes sclerostin, a member of Dan family glycoproteins, was originally identified as the gene responsible for two sclerosing bone dysplasias, sclerosteosis and van Buchem disease. "
9.	Cathepsin KIBA 06/01/2016 - "In this article, we review three rare skeletal disorders with case descriptions, pycnodysostosis and the craniotubular hyperostoses sclerosteosis and van Buchem disease that led to the development of cathepsin K and sclerostin inhibitors, respectively, for the treatment of osteoporosis. "
10.	RANK LigandIBA 10/01/2008 - "Finally, several of our specific-linkage areas encompass prominent candidate genes: type 1 collagen (COL1A1) and the sclerosteosis/van Buchem disease (SOST) genes on 17q21-23; the low-density lipoprotein receptor-related protein 5 (LRP5) gene on 11q12-13; and the rank ligand gene on 13q12-14. "

Therapies and Procedures

1.

Therapeutics 07/01/2021 - "This study investigated the effectiveness of sclerostin replacement therapy in a mouse model of sclerosteosis. " 12/01/2019 - "In the present study, we undertook dimensional and volumetric measurements in the skulls of growing Brtl/+ OI mice treated with Scl-Ab to examine whether therapy-induced phenotypic changes were similar to those observed clinically in patients with sclerosteosis or Van Buchem disorder. " 08/01/2010 - "The restricted expression pattern of sclerostin in the skeleton and the exclusive bone phenotype of good quality of patients with sclerosteosis and van Buchem disease provide the basis for the design of therapeutics that stimulate bone formation. " 06/01/2005 - "The exclusive bone phenotype of good quality of patients with sclerosteosis and Van Buchem disease and the specific localization of sclerostin make it an attractive target for the development of bone forming therapeutics." 01/01/2005 - "The restricted expression of sclerostin and the exclusive bone phenotype of good quality of patients with sclerosteosis or Van Buchem disease provide the basis for the development of therapeutics that stimulate bone formation, such as, for example, an antibody against sclerostin."