A c.1244G A (p.Arg415Gln) mutation in SH3BP2 gene causes cherubism in a Turkish family: Report of a family with review of the literature

Abstract

Objectives: The present study was aimed at advancing the understanding of the pathogenesis of cherubism by presenting a case study based on history, physical examination, typical radiological features, molecular and histopathological laboratory tests and a review of the literature. Study Design: This study began with a 7-year-old boy who was referred due to mandibular overgrowth. A panoramic radiograph revealed multilocular radiolucent lesions of the upper/lower jaws suggestive of cherubism. Overall, a total of four family members were tested for SH3BP2 mutations, namely two siblings and their parents. Both siblings had been clinically diagnosed with cherubism; however, the parents were clinically normal. Peripheral blood was collected from all participants and genomic DNA sequencing was carried out. Results: A missense mutation was found in the two affected siblings and their asymptomatic mother. The mutation was a 1244 G>A transversion which resulted in an amino acid substitution from arginine to glutamine (p.Arg415Gln) in exon 9. Conclusions: The present study emphasized the importance of further clinical and molecular investigation even when only a single case of cherubism is identified within a family. Genotype-phenotype association studies in individuals with cherubism are necessary to provide important insights into the molecular mechanisms associated with this disease. Key words:Cherubism, mandible, maxilla, SH3BP2, gene analysis, CBCT.

Clinical and genetic analysis of patients with cherubism

“…SH3BP2 product was initially identified as a c‐Abl‐binding protein in mice and humans, and despite its presence in most of the human cells, cherubism lesions are intriguingly restricted to the jaws, also carrying a temporal clinical manifestation (Fan et al., ; Reichenberger et al., ). Different mutations affecting SH3BP2 have been described in literature, and all alterations found in this study (R415Q, P418T, and P418H) had already been described before, all of them involving exon 9 (Sangu et al., ; Sekerci et al., ). As found in one case of this sample, Prescott et al.…”

“…have been described in literature, and all alterations found in this study (R415Q, P418T, and P418H) had already been described before, all of them involving exon 9 (Sangu et al, 2013;Sekerci et al, 2014). As found in one case of this sample, Prescott et al (2013) observed two cases in their sample not carrying SH3BP2 mutation; however, the clinicoradiographic and microscopic findings would support the diagnosis of cherubism in these cases.…”

“…Orthodontics is usually required after osseous growth is completed, and dental prosthesis may improve chewing ability and patients’ self‐esteem. For severe cases, surgical procedures may be necessary either for esthetic or for functional reasons (Meng et al., ), but it is important to consider that many cases are expected to regress spontaneously after puberty (Sekerci et al., ). In our sample, only 1 case exhibited complete remission (in a 36‐year‐old patient), whereas the lesion remained stable in seven patients (usually adolescents) and progressed in other six (usually children), possibly due to the patients age in the moment of their last follow‐up.…”

Clinicopathologic and Molecular Characteristics of Familial Cherubism with Associated Odontogenic Tumorous Proliferations

“…The bilateral, multilocular cystic lesions traditionally affect the posterior portion of the jaws and progress until puberty, when spontaneous clinical regression is usually observed [3,4,20]. However, unusual examples of actively expanding lesions beyond puberty, or late reactivation, have been previously reported [21,22]. In the clinicopathologic study of 24 cases of cherubism by Meng et al [9], 3/24 (12.5%) patients were older than 21 years during the onset of the disease.…”

Unusual Characteristics and Variable Expressivity in a Brazilian Family with Cherubism

“…Similar incidents have been reported previously. 35,36 Reduced penetrance happens when some individuals have specific variants and do not show the clinical features of the disease, while other individuals carrying the same variants exhibit the symptoms. These phenomena usually occur when disorders have an autosomal-dominant trait, as is the case of cherubism.…”