Genetic and Functional Analysis of Cherubism

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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Identification of Mutations That Lead to Cherubism in Families and Isolated Cases and Studies of Cellular and Molecular Mechanisms

Conditions
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Cherubism

Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of genetic elements | The goal is to identify relevant genes or genetic elements that cause the disease or contribute to the disease progression and severity. | at time of identification | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cherubism, bone, autoinflammatory disorder, osteoblast, osteoclast, mandible, maxilla