背景:家族性巨型牙骨质瘤(FGC)是一种罕见的肿瘤,其特征是颌骨多象限纤维骨病变的早期发作,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最终表现出逐步快速增长,但尚未发现可疑的致病基因。
方法:在本研究中,招募了三名FGC患者,从肿瘤组织和外周血中提取基因组DNA进行全外显子组测序。
结果:结果显示,所有三名患者均具有杂合突变c.1067G>A(p。Cys356Tyr)在ANO5基因中。此外,在这个位点ANO5中的常染色体显性突变已在颌骨骨干发育不良(GDD)患者中被鉴定出来,并被认为是潜在的致病因子。提示FGC和GDD之间的遗传关联。此外,检测到具有相似临床表现的多灶性纤维骨病变,包括5例花状骨水泥骨发育不良,5例多孔纤维发育不良,和8例青少年骨化纤维瘤;然而,它们都不存在ANO5基因突变。
结论:我们的发现表明FGC可能是GDD的非典型变体,为ANO5基因检测作为多象限复杂病例辅助诊断方法的可行性提供证据。
BACKGROUND: 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.
METHODS: 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: 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.
CONCLUSIONS: 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.