Novel mutations in the <i>SH3BP2</i> gene associated with sporadic central giant cell lesions and cherubism

Carvalho, VM; Perdigão, Paôlla Freitas; Amaral, FR; Souza, Pea de; Marco, Luiz; Gomez, Ricardo Santiago

doi:10.1111/j.1601-0825.2008.01499.x

Cited by 46 publications

(45 citation statements)

References 31 publications

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“…After RANKL signaling, a complex containing a SH3BP2 second messenger is involved in a calcineurin cascade that activates NFATc1, increasing osteoclastogenesis and giant cell formation (11). SH3BP2 is mutated in cherubism, and it was further demonstrated that this gene is also mutated in CGCL (9).…”

Section: Discussionmentioning

confidence: 99%

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Increased expression of NFATc1 in giant cell lesions of the jaws, cherubism and brown tumor of hyperparathyroidism

et al. 2011

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Abstract.A variety of diseases of the jaws may present multinucleated giant cells. These diseases include central giant cell lesions (CGCL), peripheral giant cell lesions (PGCL), brown tumor of hyperparathyroidism (BTH), and cherubism. The multinucleated giant cells in these lesions are osteoclast-like. Since NFATc1 plays a significant role in osteoclast differentiation, the present study aimed to compare the expression of NFATc1 in CGCL, PGCL, BTH and cherubism. A total of 14 formalin-fixed and paraffin-embedded tissue samples of CGCL (n=4), PGCL (n=5), BTH (n=3) and cherubism (n=2) were included in the study. An immunohistochemical analysis was performed to investigate the NFATc1 protein.The majority of giant cells in all of the cases were positive for nuclear NFATc1 and the immunostaining pattern was similar in all of the groups. Although our study supports the hypothesis that giant cell accumulation in PGCL, CGCL, BTH and cherubism is mediated by NFATc1, functional studies are required to investigate this hypothesis.

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Section: Discussionmentioning

confidence: 99%

“…Missense mutations were observed in the SH3BP2 gene mainly clustered in exon 9, which encodes a proline-rich region of the protein (7,8). Recently, a somatic mutation of this gene was described in a case of CGCL (9).…”

Section: Introductionmentioning

confidence: 99%

Increased expression of NFATc1 in giant cell lesions of the jaws, cherubism and brown tumor of hyperparathyroidism

et al. 2011

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“…Regarding etiology, which is a much debated topic, there are local and systemic factors as well as possible mutations described in exons 3, 4, 9 and 11 of SH3BP2 gene (5,35) . Nevertheless, the study by Teixeira et al (35) only found associations with exon 4 and the remaining ones would be more related to cherubism.…”

Section: Central Giant Cell Lesionsmentioning

confidence: 99%

Peripheral and central giant cell lesions: etiology, origin of giant cells, diagnosis and treatment

Vasconcelos

Vasconcelos²,

Queiroz

2013

J. Bras. Patol. Med. Lab.

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Introduction and objective: The peripheral and central giant cell lesions (PGCL and CGCL) are a group of pathological entities with similar histopathological features and whose origin has not been fully elucidated. The former is reactive and the latter exhibits a nonneoplastic proliferative behavior. This article aims to review the literature on peripheral giant cell lesions (PGCL) and central giant cell lesions (CGCL) by discussing the most important aspects pertaining to each of them. Results: These lesions are found in different locations and show diverse clinical signs despite having the same histopathological features. The treatment consists in the surgical resection by different techniques depending on the type of the lesion and clinical conditions. In the case of CGCL, drug therapy may also be employed. Conclusion: Although there is no consensus in the literature, it is essential to know the etiology of these lesions as well as the exact origin of the giant cells. Due to their singular biological behavior, it is of utmost importance to establish a differential diagnosis between the two lesions and other processes that have similar clinical, radiological and histological characteristics, inasmuch as this procedure is essential to provide a suitable treatment and establish a prognosis.

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“…This mutation was first reported by Ueki et al [2001] in a family with a classical cherubic phenotype. It is described in the well-known mutation hotspot at amino acid number 415 to 420 [Ueki et al, 2001;Lo et al, 2003;de Lange et al, 2007;Carvalho et al, 2009]. All 11 missense mutations identified so far are in exon 9 and affect 4 amino acids within a 6-amino acid sequence (RSPPDG) located 31 to 36 amino acids upstream of the SH2 domain and 205 to 210 downstream of the SH3-binding domain [Ueki et al, 2001;Lo et al, 2003;Lietman et al, 2006].…”

Section: Discussionmentioning

confidence: 99%

Identical Mutation in SH3BP2 Gene Causes Clinical Phenotypes with Different Severity in Mother and Daughter – Case Report

Preda

Dincă²,

Bucur³

et al. 2010

Mol Syndromol

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Cherubism is a particular form of fibrous dysplasia of the jaws. Familial occurrence was reported in most cases. The condition is a rare hereditary disorder with autosomal dominant inheritance, with complete penetrance in males and incomplete penetrance in females and variable expressivity. It is known to be caused by mutations in the gene encoding SH3-domain binding protein 2, SH3BP2 gene. Major diagnostic criteria are cherubic facial appearance, painless hard enlargement of the jaws, and frequently associated dental abnormalities. The aim of the study was to analyze clinical and genetic features of cherubism in a family with 3 daughters in which the youngest one was affected. Clinical and radiographic examinations, hematological and biochemical evaluations and biopsy were performed. Molecular genetic analysis consisted of PCR amplification and direct sequencing of selected exons of the SH3BP2 gene. Cherubism was suspected based on clinical and radiographic examinations of the 9-year-old daughter. She presented asymmetrical enlargement of the mandible, speech and swallowing problems and dental abnormalities on the lower jaw. There was no history of similar clinical findings in any of the daughters or the parents of the affected girl. Abnormal results were obtained by genetic analysis. A c.1244G>A mutation was identified in exon 9 of the SH3BP2 gene in the asymptomatic mother and her affected daughter. The identified mutation in the SH3BP2 gene is probably disease-causing. The asymptomatic mother transmitted the gene mutation to her affected daughter. Our results confirm the reduced penetrance and variable expression of the gene mutation.

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Novel mutations in the SH3BP2 gene associated with sporadic central giant cell lesions and cherubism

Cited by 46 publications

References 31 publications

Increased expression of NFATc1 in giant cell lesions of the jaws, cherubism and brown tumor of hyperparathyroidism

Increased expression of NFATc1 in giant cell lesions of the jaws, cherubism and brown tumor of hyperparathyroidism

Peripheral and central giant cell lesions: etiology, origin of giant cells, diagnosis and treatment

Identical Mutation in SH3BP2 Gene Causes Clinical Phenotypes with Different Severity in Mother and Daughter – Case Report

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