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Genetic and Functional Analysis of Cherubism (CBM)

This study is currently recruiting participants.
Verified September 2016 by Ernst Reichenberger, University of Connecticut Health Center
ClinicalTrials.gov Identifier:
First Posted: June 28, 2012
Last Update Posted: September 9, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Ernst Reichenberger, University of Connecticut Health Center
The goal of this research study is to identify genes and regulatory elements on chromosomes that cause cherubism. Together with the investigators collaborators the investigators also study blood samples and tissue samples from patients to learn about the processes that lead to this disorder. The long-term goal of researchers involved in this study is to find mechanisms to slow down bone resorption in cherubism patients.


Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Identification of Mutations That Lead to Cherubism in Families and Isolated Cases and Studies of Cellular and Molecular Mechanisms

Resource links provided by NLM:

Further study details as provided by Ernst Reichenberger, University of Connecticut Health Center:

Primary Outcome Measures:
  • Identification of genetic elements [ Time Frame: at time of identification ]
    The goal is to identify relevant genes or genetic elements that cause the disease or contribute to the disease progression and severity.

Biospecimen Retention:   Samples With DNA
Saliva, blood, bone tissue

Estimated Enrollment: 600
Study Start Date: April 2009
Estimated Study Completion Date: December 2025
Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)
Detailed Description:

Cherubism is a very rare bone disorder where bone gets excessively resorbed only in the jaw bones (mandible and maxilla). The resulting cavities in bone fill up with soft fibrous (fibro-osseous) tissues that can expand and push the bony shells apart. Thus the characteristic facial appearance in patients with progressed cherubism. Bone resorption (cherubism lesions) in this disorder occurs always symmetrically in the mandible, the maxilla or in both. This distinguishes cherubism from similar disorders. As cherubism progresses, the lesions can invade the eye sockets (inferior and/or lateral orbital walls) and displace the eye balls and push down the eyelids. As a result the sclera (white of the eye) below the iris becomes visible and patients have an upward gazing appearance (cherubic look) which gave the name to this fibro-proliferative bone disorder.

Cherubism typically appears between ages of 2-7 years. It is often diagnosed during dental evaluations. At early stages cherubism is accompanied by lymph node swelling. Proliferation of the fibro-osseous tissue typically stops after puberty and in many the soft tissue in the cherubic bone cavities are replaced by new bone.

For this study we will:

  • Send out study participation kits and consent by phone
  • Collect a saliva sample from eligible individuals
  • Obtain information regarding cherubism
  • Document disorder with photos and doctor's letters
  • If patients undergo surgery for cherubism we ask to obtain some bone tissue that would otherwise be discarded
  • Isolate DNA from the saliva sample
  • Perform genetic analyses of the DNA with the most up-to-date methods available to identify genetic variations
  • Study in the laboratory why the genetic variations cause the disorder

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Individuals with clinically diagnosed cherubism

Inclusion Criteria:

  • cherubism; unaffected individuals only if part of a participating cherubism family

Exclusion Criteria:

  • no cherubism unaffected individuals only as part of a participating cherubism family
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01630447

Contact: Ernst J Reichenberger, PhD 860-679-2062 reichenberger@uchc.edu

United States, Connecticut
University of Connecticut Health Center Recruiting
Farmington, Connecticut, United States, 06030
Contact: Ernst J Reichenberger, PhD    860-679-2062    reichenberger@uchc.edu   
Sponsors and Collaborators
UConn Health
Principal Investigator: Ernst J Reichenberger, PhD UConn Health
  More Information

Additional Information:
Ueki Y, Tiziani V, Santanna C, Fukai N, Maulik C, Garfinkle J, Ninomiya C, doAmaral C, Peters H, Habal M, Rhee-Morris L, Doss JB, Kreiborg S, Olsen BR, Reichenberger E. Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism. Nat Genet. 2001 Jun;28(2):125-6.
Gilbert G, Défillo M, Delcan JL, David P. [Results of anastomoses in the tetralogy of Fallot]. Union Med Can. 1966 Dec;95(12):1377-84. French.
Ueki Y, Lin CY, Senoo M, Ebihara T, Agata N, Onji M, Saheki Y, Kawai T, Mukherjee PM, Reichenberger E, Olsen BR. Increased myeloid cell responses to M-CSF and RANKL cause bone loss and inflammation in SH3BP2 "cherubism" mice. Cell. 2007 Jan 12;128(1):71-83.
Wang CJ, Chen IP, Koczon-Jaremko B, Boskey AL, Ueki Y, Kuhn L, Reichenberger EJ. Pro416Arg cherubism mutation in Sh3bp2 knock-in mice affects osteoblasts and alters bone mineral and matrix properties. Bone. 2010 May;46(5):1306-15. doi: 10.1016/j.bone.2010.01.380. Epub 2010 Feb 1.
Levaot N, Simoncic PD, Dimitriou ID, Scotter A, La Rose J, Ng AH, Willett TL, Wang CJ, Janmohamed S, Grynpas M, Reichenberger E, Rottapel R. 3BP2-deficient mice are osteoporotic with impaired osteoblast and osteoclast functions. J Clin Invest. 2011 Aug;121(8):3244-57. doi: 10.1172/JCI45843. Epub 2011 Jul 18.
Reichenberger EJ, Levine MA, Olsen BR, Papadaki ME, Lietman SA. The role of SH3BP2 in the pathophysiology of cherubism. Orphanet J Rare Dis. 2012 May 24;7 Suppl 1:S5. doi: 10.1186/1750-1172-7-S1-S5. Epub 2012 May 24. Review.
Papadaki ME, Lietman SA, Levine MA, Olsen BR, Kaban LB, Reichenberger EJ. Cherubism: best clinical practice. Orphanet J Rare Dis. 2012 May 24;7 Suppl 1:S6. doi: 10.1186/1750-1172-7-S1-S6. Epub 2012 May 24. Review.
Levaot N, Voytyuk O, Dimitriou I, Sircoulomb F, Chandrakumar A, Deckert M, Krzyzanowski PM, Scotter A, Gu S, Janmohamed S, Cong F, Simoncic PD, Ueki Y, La Rose J, Rottapel R. Loss of Tankyrase-mediated destruction of 3BP2 is the underlying pathogenic mechanism of cherubism. Cell. 2011 Dec 9;147(6):1324-39. doi: 10.1016/j.cell.2011.10.045.

Responsible Party: Ernst Reichenberger, Assoc. Prof., University of Connecticut Health Center
ClinicalTrials.gov Identifier: NCT01630447     History of Changes
Other Study ID Numbers: UCHC03-008CBM
First Submitted: June 25, 2012
First Posted: June 28, 2012
Last Update Posted: September 9, 2016
Last Verified: September 2016

Keywords provided by Ernst Reichenberger, University of Connecticut Health Center:
autoinflammatory disorder

Additional relevant MeSH terms:
Fibrous Dysplasia of Bone
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Jaw Diseases
Stomatognathic Diseases
Maxillofacial Abnormalities
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn

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