Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
Mol Genet Genomic Med. 2024 Jan;12(1):e2277. doi: 10.1002/mgg3.2277. Epub 2023 Aug 30.
Familial gigantiform cementoma (FGC) is a rare tumor characterized by the early onset of multi-quadrant fibro-osseous lesions in the jaws, causing severe maxillofacial deformities. Its clinicopathological features overlap with those of other benign fibro-osseous lesions. FGC eventually exhibits progressively rapid growth, but no suspected causative gene has been identified.
In this study, three patients with FGC were recruited, and genomic DNA from the tumor tissue and peripheral blood was extracted for whole-exome sequencing.
Results showed that all three patients harbored the heterozygous mutation c.1067G > A (p.Cys356Tyr) in the ANO5 gene. Furthermore, autosomal dominant mutations in ANO5 at this locus have been identified in patients with gnathodiaphyseal dysplasia (GDD) and are considered a potential causative agent, suggesting a genetic association between FGC and GDD. In addition, multifocal fibrous bone lesions with similar clinical presentations were detected, including five cases of florid cemento-osseous dysplasia, five cases of polyostotic fibrous dysplasia, and eight cases of juvenile ossifying fibromas; however, none of them harbored mutations in the ANO5 gene.
Our findings indicate that FGC may be an atypical variant of GDD, providing evidence for the feasibility of ANO5 gene testing as an auxiliary diagnostic method for complex cases with multiple quadrants.
家族性巨颌牙骨质瘤（FGC）是一种罕见的肿瘤，其特征为颌骨多象限纤维骨性病变的早期发病，导致严重的颌面部畸形。其临床病理特征与其他良性纤维骨性病变重叠。FGC 最终表现为逐渐快速生长，但尚未发现可疑的致病基因。
本研究招募了 3 名 FGC 患者，提取肿瘤组织和外周血的基因组 DNA 进行全外显子组测序。
结果表明，所有 3 名患者均携带 ANO5 基因 c.1067G>A（p.Cys356Tyr）杂合突变。此外，该部位的 ANO5 常染色体显性突变已在颌骨骨发育不良（GDD）患者中被发现，被认为是一个潜在的致病因素，提示 FGC 与 GDD 之间存在遗传关联。此外，还检测到具有相似临床表现的多灶性纤维骨病变，包括 5 例骨纤维异常增殖症、5 例多骨纤维异常增殖症和 8 例骨化性纤维瘤；然而，它们都没有 ANO5 基因突变。
我们的研究结果表明，FGC 可能是 GDD 的一种非典型变异，为 ANO5 基因突变检测作为多象限复杂病例的辅助诊断方法提供了证据。
