Gnathodiaphyseal Dysplasia: report of a rare case with a de novo insertion mutation of ANO5 gene and review of the literature.

IF 2 3区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE
Prof Christos Yapijakis , Prof Evangelia Pιperi , Dr. Konstantinos Tzanavaris , Dr. Efstathios Pettas , Prof. Maria Georgaki , Prof. Nikolaos G. Nikitakis
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引用次数: 0

Abstract

Introduction

Gnathodiaphyseal dysplasia (GDD) is a rare autosomal dominant disorder caused by point mutations in anoctamin 5 (ANO5) gene (11p14.3), characterized by sclerosis of the tubular bones and benign fibro-osseous (BFO) lesions of the jaws. GDD may also occur sporadically due to missense mutations, while de novo ANO5 insertion mutations have only been rarely described.

Case description

A 10-year-old boy presented for evaluation of asymptomatic radiopaque lesions involving the posterior mandible, bilaterally. Multiple bone biopsies were performed with features of BFO. Sequential imaging with panoramic radiographs and cone beam computer tomography scans for the next 3 years revealed that the lesions gradually increased in size, whereas multiple new distinct hyperdense areas with relatively well-defined borders throughout both jaws were observed. Eventually, painful symptoms developed in the area of the left TMJ, associated with the development of lesions in the left mandibular condyle. Genetic evaluation of the patient's family history of four generations did not render evidence of a hereditary condition, while craniognathic radiographic examination of both parents was normal. Further molecular investigation with Whole Exome Sequencing in DNA isolated from a whole blood sample detected a heterozygous insertion mutation in the ANO5 gene. Taken together, a final diagnosis of GDD with a de novo ANO5 mutation was rendered.

Conclusions

GDD is characterized by genetic disruption of ANO5, a calcium-activated chloride channel, usually caused by inherited single amino-acid substitutions, resulting in impaired osteoclastogenesis. GDD with a de novo insertion mutation in ANO5, as in our case, has been described only once before. The exact pathogenesis of GDD remains unclear, necessitating further studies to elucidate the whole genetic and phenotypic spectrum of the disorder. A multidisciplinary approach to diagnosis with involvement of oral and maxillofacial pathologists, radiologists and geneticists is mandatory.

骺软骨发育不良:一例罕见的 ANO5 基因新插入突变病例报告及文献综述。
导言骺软骨发育不良(GDD)是一种罕见的常染色体显性遗传疾病,由anoctamin 5(ANO5)基因(11p14.3)的点突变引起,以管状骨硬化和颌骨良性纤维骨病(BFO)为特征。GDD 也可能因错义突变而偶发,而新的 ANO5 插入突变仅在极少数情况下被描述过。病例描述:一名 10 岁男孩因双侧下颌骨后部出现无症状不透射线的病变而前来就诊。进行了多处骨活检,结果显示有 BFO 特征。在接下来的三年中,通过全景X光片和锥形束计算机断层扫描进行的连续成像显示,病变逐渐增大,同时在整个下颌骨中观察到多个边界相对清晰的新的明显高密度区。最后,左侧颞下颌关节部位出现疼痛症状,与左侧下颌骨髁状突病变有关。对患者四代家族史的遗传学评估没有发现遗传性疾病的证据,而父母双方的颅颌面放射学检查均正常。通过对从全血样本中分离出的 DNA 进行全外显子组测序进行进一步的分子研究,发现 ANO5 基因存在杂合插入突变。结论GDD 的特征是 ANO5(一种钙激活的氯离子通道)基因紊乱,通常由遗传性单氨基酸置换引起,导致破骨细胞生成受损。像我们的病例一样,ANO5 发生新插入突变的 GDD 之前仅被描述过一次。GDD 的确切发病机制仍不清楚,需要进一步研究以阐明该疾病的整个遗传和表型谱。口腔颌面病理学家、放射学专家和遗传学家必须参与多学科诊断。
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来源期刊
Oral Surgery Oral Medicine Oral Pathology Oral Radiology
Oral Surgery Oral Medicine Oral Pathology Oral Radiology DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
3.80
自引率
6.90%
发文量
1217
审稿时长
2-4 weeks
期刊介绍: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology is required reading for anyone in the fields of oral surgery, oral medicine, oral pathology, oral radiology or advanced general practice dentistry. It is the only major dental journal that provides a practical and complete overview of the medical and surgical techniques of dental practice in four areas. Topics covered include such current issues as dental implants, treatment of HIV-infected patients, and evaluation and treatment of TMJ disorders. The official publication for nine societies, the Journal is recommended for initial purchase in the Brandon Hill study, Selected List of Books and Journals for the Small Medical Library.
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