Zong Yanfang, Liu Wei, Hou Cuilan, Zhang Han, Jiang Xunwei, Sun Xiaomin, Xie Lijian, Xiao Tingting, Zhang Yongwei, Li Yun
Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Transl Pediatr. 2021 Aug;10(8):2123-2130. doi: 10.21037/tp-20-156.
Hereditary hemorrhagic telangiectasis (HHT) is an autosomal dominant vascular disease, and approximately 80% of all HHT cases are caused by gene mutation. In this report, we analyzed the case of an 11-year-old girl who had intracranial bleeding when she was 7 years old. Her brain computed tomography (CT) scans and craniocerebral angiography results revealed that she had multiple cerebral arteriovenous malformations (CAVMs). Cardiac computed tomography angiography (CTA) revealed a pulmonary arteriovenous malformation (PAVM) located in a segment of the left lung. This patient's primary diagnosis was of CAVMs and PAVMs. Both cerebral vascular embolization therapy and interventional treatment for PAVMs were performed to treat these respective conditions. The operations were successful and the patient's prognosis was good. To confirm the patient's diagnosis and the cause of her conditions, peripheral blood was collected from her and her family for whole-exome sequencing (WES). Sanger sequencing was used to verify these results and STRUM software was used to predict the presence of mutant proteins. We found a new mutation of the endoglin (ENG) gene present in this family; this mutation is known as c.1466del (p.Gln489Argfs2). The patient's mother was a carrier of this heterozygous mutation. STRUM software confirmed that the configuration of the ENG protein p.Gln489Argfs2 site changed with this mutation. We believe this c.1466del (p.Gln489Argfs2) mutation affects ENG protein function, and the resultant ENG protein dysfunction leads to HHT. When a child has multiple vascular malformation, HHT should be considered as a primary diagnosis.
遗传性出血性毛细血管扩张症（HHT）是一种常染色体显性血管疾病，所有HHT病例中约80%由基因突变引起。在本报告中，我们分析了一名11岁女孩的病例，她7岁时发生颅内出血。她的脑部计算机断层扫描（CT）和脑血管造影结果显示，她患有多处脑动静脉畸形（CAVM）。心脏计算机断层扫描血管造影（CTA）显示左肺一段有肺动静脉畸形（PAVM）。该患者的初步诊断为CAVM和PAVM。分别对这些病症进行了脑血管栓塞治疗和PAVM介入治疗。手术成功，患者预后良好。为了确诊患者的病情及其病因，采集了她及其家人的外周血进行全外显子组测序（WES）。使用桑格测序法验证这些结果，并使用STRUM软件预测突变蛋白的存在。我们在这个家族中发现了内皮糖蛋白（ENG）基因的一个新突变；这个突变被称为c.1466del（p.Gln489Argfs2）。患者的母亲是这种杂合突变的携带者。STRUM软件证实，ENG蛋白p.Gln489Argfs2位点的结构因该突变而改变。我们认为这种c.1466del（p.Gln489Argfs2）突变影响ENG蛋白功能，由此产生的ENG蛋白功能障碍导致了HHT。当儿童患有多处血管畸形时，应将HHT作为初步诊断。
