RUNX2 Quadruplication

Greives, Timothy J.; Odessey, Eric; Waggoner, Darrel; Shenaq, Deana; Aradhya, Swaroop; Mitchell, Allison; Whitcomb, Emma; Warshawsky, Neil; He, Tong Chuan; Reid, Russell R.

doi:10.1097/scs.0b013e31826686d3

Cited by 18 publications

(5 citation statements)

References 11 publications

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“…RUNX2 deficiency results in deficient skull ossification in the context of cleidocranial dysplasia. Importantly, RUNX2 duplication [Mefford et al, 2010], triplication [Varvagiannis et al, 2013] and quadruplication [Greives et al, 2013] have been reported in patients with syndromic CS and there appears to be a direct correlation between the gene copy number and the severity of the phenotype. Our group identified two rare missense variants, M175R and R237C in two of 137 patients with sNCS.…”

Section: Genetic Etiopathogenesis Of Craniosynostosismentioning

confidence: 99%

Genetic advances in craniosynostosis

Lattanzi

Barba

Pietro

et al. 2017

American J of Med Genetics Pt A

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Craniosynostosis, the premature ossification of one or more skull sutures, is a clinically and genetically heterogeneous congenital anomaly affecting approximately 1 in 2,500 live births. In most cases, it occurs as an isolated congenital anomaly, i.e. nonsyndromic craniosynostosis (NCS), the genetic and environmental causes of which remain largely unknown. Recent data suggest that at least some of the midline NCS cases may be explained by two loci inheritance. In approximately 25–30% of patients craniosynostosis presents as a feature of a genetic syndrome due to chromosomal defects or mutations in genes within interconnected signaling pathways. The aim of this review is to provide a detailed and comprehensive update on the genetic and environmental factors associated with NCS, integrating the scientific findings achieved during the last decade. Focus on the neurodevelopmental, imaging and treatment aspects of NCS is also provided.

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Section: Genetic Etiopathogenesis Of Craniosynostosismentioning

confidence: 99%

Genetic advances in craniosynostosis

Lattanzi

Barba

Pietro

et al. 2017

American J of Med Genetics Pt A

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“… 46 In craniosynostosis, additional copies of Runx2 have been detected in a small number of individuals causing pansynostosis and significant midface hypoplasia. 47 …”

Section: Signaling Bone Formationmentioning

confidence: 99%

Signaling pathways in osteogenesis and osteoclastogenesis: Lessons from cranial sutures and applications to regenerative medicine

2015

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One of the simplest models for examining the interplay between bone formation and resorption is the junction between the cranial bones. Although only roughly a quarter of patients diagnosed with craniosynostosis have been linked to known genetic disturbances, the molecular mechanisms elucidated from these studies have provided basic knowledge of bone homeostasis. This work has translated to methods and advances in bone tissue engineering. In this review, we examine the current knowledge of cranial suture biology derived from human craniosynostosis syndromes and discuss its application to regenerative medicine.

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“…These findings suggest that the range of bone phenotypes observed in CCD patients could be due to a quantitative reduction in the functional activity of RUNX2. By contrast a higher gene dosage due to mutations with excess copy of RUNX2 also causes craniosynostosis (CS) syndrome (Greives et al, 2013; Mefford et al, 2010), an opposite extreme syndrome for bone development compared to CCD. CS causes premature mineralization of the bone growth areas including suture and hypertrophic zone of long bones.…”

Section: Introductionmentioning

confidence: 99%

Pin1‐mediated Runx2 modification is critical for skeletal development

Yoon

Islam

Cho

et al. 2013

Journal Cellular Physiology

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Runx2 is the master transcription factor for bone formation. Haploinsufficiency of RUNX2 is the genetic cause of cleidocranial dysplasia (CCD) that is characterized by hypoplastic clavicles and open fontanels. In this study, we found that Pin1, peptidyl prolyl cis-trans isomerase, is a critical regulator of Runx2 in vivo and in vitro. Pin1 mutant mice developed CCD-like phenotypes with hypoplastic clavicles and open fontanels as found in the Runx2+/− mice. In addition Runx2 protein level was significantly reduced in Pin1 mutant mice. Moreover Pin1 directly interacts with the Runx2 protein in a phosphorylation-dependent manner and subsequently stabilizes Runx2 protein. In the absence of Pin1, Runx2 is rapidly degraded by the ubiquitin-dependent protein degradation pathway. However, Pin1 overexpression strongly attenuated uniquitin-dependent Runx2 degradation. Collectively conformational change of Runx2 by Pin1 is essential for its protein stability and possibly enhances the level of active Runx2 in vivo.

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RUNX2 Quadruplication

Cited by 18 publications

References 11 publications

Genetic advances in craniosynostosis

Genetic advances in craniosynostosis

Signaling pathways in osteogenesis and osteoclastogenesis: Lessons from cranial sutures and applications to regenerative medicine

Pin1‐mediated Runx2 modification is critical for skeletal development

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