Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital, Guangzhou, China.
Head Neck. 2019 Jan;41(1):230-238. doi: 10.1002/hed.25516. Epub 2018 Dec 15.
Gnathodiaphyseal dysplasia (GDD) is a rare skeletal disorder that has not been well studied.
Sanger sequencing, whole-genome sequencing (WGS), and bioinformatics and structural modeling analyses were performed.
A family with patients with fibro-osseous lesions of the jawbones were initially diagnosed with cherubism. Sequencing of SH3BP2, which is the causal gene of cherubism, revealed no pathogenic mutation. Through WGS, we identified a novel mutation c.1067G>T (p.C356F) in ANO5, and bioinformatics analyses and structural modeling showed that the mutation was deleterious. Because ANO5 is the gene responsible for GDD, we reappraised the clinical data of the patients, and the diagnosis was corrected to atypical GDD. A review of the literature showed that 67% of GDD cases confirmed by molecular testing were initially misdiagnosed.
The novel mutation c.1067G>T (p.C356F) in ANO5 is responsible for the atypical GDD observed in our patients. GDD should be included in the differential diagnosis for patients with fibro-osseous lesions.
颌骨牙骨质发育不良（GDD）是一种罕见的骨骼疾病，尚未得到充分研究。
进行了 Sanger 测序、全基因组测序（WGS）以及生物信息学和结构建模分析。
一个颌骨纤维骨性病变的患者家系最初被诊断为 cherubism。对 cherubism 的致病基因 SH3BP2 进行测序未发现致病性突变。通过 WGS，我们在 ANO5 中鉴定出一个新的突变 c.1067G>T（p.C356F），生物信息学分析和结构建模表明该突变是有害的。由于 ANO5 是导致 GDD 的基因，我们重新评估了患者的临床数据，将诊断修正为非典型 GDD。文献复习显示，67%经分子检测证实的 GDD 病例最初被误诊。
ANO5 中的新型突变 c.1067G>T（p.C356F）导致了我们观察到的非典型 GDD。对于患有纤维骨性病变的患者，应将 GDD 纳入鉴别诊断。
