Osteopathia striata with cranial sclerosis owing to <i>WTX</i> gene defect

Perdu, Bram; Freitas, Fenna de; Frints, Suzanna G.M.; Schouten, Meyke; Schrander‐Stumpel, Connie; Barbosa, Mafalda; Pinto‐Basto, Jorge; Reis-Lima, Margarida; Vernejoul, Marie‐Christine de; Becker, Kristin; Freckmann, Marie-Louise; Keymolen, Kathelijn; Haan, Eric; Savarirayan, Ravi; Koenig, Rainer; Zabel, Bernhard; Vanhoenacker, Filip; Hul, Wim Van

doi:10.1359/jbmr.090707

Cited by 68 publications

(100 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the already mentioned mutations in the co-receptor LRP5 and the Wnt inhibitor sclerostin, mutations were found in WTX, a member of the destruction complex of b-catenin, causing osteopathia striata (132,133,134). Furthermore, a loss-of-function mutation in LRP6 results in a condition with osteoporosis, coronary artery diseases, and metabolic syndrome (135).…”

Section: The Involvement Of the Canonical Wnt Signaling Pathway In Bomentioning

confidence: 99%

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

Bollerslev

Henriksen

Nielsen

et al. 2013

European Journal of Endocrinology

View full text Add to dashboard Cite

Systematic studies of autosomal dominant osteopetrosis (ADO) were followed by the identification of underlying mutations giving unique possibilities to perform translational studies. What was previously designated ADO1 turned out to be a high bone mass phenotype caused by a missense mutation in the first propeller of LRP5, a region of importance for binding inhibitory proteins. Thereby, ADO1 cannot be regarded as a classical form of osteopetrosis but must now be considered a disease of LRP5 activation. ADO (Albers-Schönberg disease, or previously ADO2) is characterized by increased number of osteoclasts and a defect in the chloride transport system (ClC-7) of importance for acidification of the resorption lacuna (a form of Chloride Channel 7 Deficiency Osteopetrosis). Ex vivo studies of osteoclasts from ADO have shown that cells do form normally but have reduced resorption capacity and an expanded life span. Bone formation seems normal despite decreased osteoclast function. Uncoupling of formation from resorption makes ADO of interest for new strategies for treatment of osteoporosis. Recent studies have integrated bone metabolism in whole-body energy homeostasis. Patients with ADO may have decreased insulin levels indicating importance beyond bone metabolism. There seems to be a paradigm shift in the treatment of osteoporosis. Targeting ClC-7 might introduce a new principle of dual action. Drugs affecting ClC-7 could be antiresorptive, still allowing ongoing bone formation. Inversely, drugs affecting the inhibitory site of LRP5 might stimulate bone formation and inhibit resorption. Thereby, these studies have highlighted several intriguing treatment possibilities, employing novel modes of action, which could provide benefits to the treatment of osteoporosis.

show abstract

Section: The Involvement Of the Canonical Wnt Signaling Pathway In Bomentioning

confidence: 99%

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

Bollerslev

Henriksen

Nielsen

et al. 2013

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Sclerosis in osteopathia striata with cranial sclerosis (OSCS) is caused by a genetic defect in the Wnt repressor gene WTX (Wilms Tumor on the X-chromosome) [25,26]. Patients with this genetic defect suffer from bone sclerosis in the long bones and cranium.…”

Section: A Sclerosis Of Subchondral Bonementioning

confidence: 99%

To Seek Shelter from the Wnt in Osteoarthritis? Wnt-Signaling as a Target for Osteoarthritis Therapy

Blom¹,

Lent²,

Kraan³

et al. 2010

CDT

View full text Add to dashboard Cite

Recent evidence from animal experiments and clinical samples points at a role for Wnt-signaling in osteoarthritis (OA) pathology. These pathways are key inducers and regulators of joint development, and are involved in formation of bone, cartilage and also synovium. Disregulation of members from this pathways have been described in OA. This makes the Wnt-family of proteins and signaling pathways an attractive target for therapy. Although knowledge is increasing rapidly it is still a challenge to decide on the best approach in targeting Wnt signaling. Activation of the canonical signaling pathway, which features intra-cellular accumulation of beta-catenin, is most often implicated in recent studies in OA pathology, in experimental OA and spondyloarthritis. However, direct targeting of beta-catenin is anticipated to be too hazardous, because of its importance for the maintenance of stability of articular chondrocyte phenotype and because of its proven role in carcinogenesis. A more attractive approach will be identifying the misexpression of specific Wnt-proteins or their inhibitors in various tissues that are important in OA, bone, cartilage and synovium, to point out targets for therapy. For example, recently it was shown that Wnt16 is strongly upregulated in cartilage after injury and in synovium in experimental OA, and the expression of this canonical Wnt may be responsible for OA-like changes. Alternatively, identifying more down stream Wnt signaling effector molecules, like WISP-1, for more specific therapy promises to be a safer and more efficient approach to find a treatment for this disease that heavily constrains millions of people each year.

show abstract

“…It also promotes the ubiquitylation and degradation of β-catenin. Both WTX isoforms are able to bind β-catenin [2,4,5,6].…”

Section: Discussionmentioning

confidence: 99%

“…If the WTX gene is mutated, WNT signaling will increase. Therefore, WTX normally acts as a repressor of canonical WNT signaling [4].…”

Section: Introductionmentioning

confidence: 99%

Prenatal Diagnosis of Osteopathia Striata with Cranial Sclerosis in a Male Fetus with a ~330kb Deletion of Xq11.1 Involving the WTX Gene

Wilson¹,

Davis²,

Goodman³

et al. 2013

AJMBR

View full text Add to dashboard Cite

Osteopathia striata with cranial sclerosis (OSCS) is a rare X-linked dominant genetic disorder resulting mutation in the WTX gene. Clinically, OSCS presents with linear striations in the metaphyseal region of the long bones and pelvis in combination with sclerosis of the cranium and face. A twenty-seven year old G5T1P3A0L2 woman with a history of peri-and neonatal infant male deaths was referred to us at 22 weeks, 6 days into her recent pregnancy. Ultrasound evaluation identified a male fetus, bilaterally enlarged lateral ventricles, a cloverleaf skull, suspected bilateral cleft lip, nuchal thickening, bilateral bowed radii and ulnae, gastroschisis with herniated viscera, bilateral absent fibula and clubfeet. The results of prenatal testing identified a male fetus with a 330kb Xq11.1 deletion involving the entire WTX gene. Initial microarray analysis of maternal blood identified a normal female karyotype, 46,XX. FISH analysis with a BAC clone mapped to the WTX gene identified low-level mosaicism in blood and buccal samples, 17% and 15%, respectively, which explained the negative maternal microarray result.

show abstract

Osteopathia striata with cranial sclerosis owing to WTX gene defect

Cited by 68 publications

References 24 publications

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

To Seek Shelter from the Wnt in Osteoarthritis? Wnt-Signaling as a Target for Osteoarthritis Therapy

Prenatal Diagnosis of Osteopathia Striata with Cranial Sclerosis in a Male Fetus with a ~330kb Deletion of Xq11.1 Involving the WTX Gene

Contact Info

Product

Resources

About