SARS2基因错义突变所致HUPRA综合征的临床特征和遗传学分析并文献复习  

Clinical and genetic analysis of a patient with HUPRA syndrome due to missense variants of SARS2 gene and literature review

作　　者：黄娟 李秋雨 吉炜 郭晓峰[4] 胡晓虹 Huang Juan;Li Qiuyu;Ji Wei;Guo Xiaofeng;Hu Xiaohong(Department of Cardiology,Fujian Children′s Hospital,Fuzhou 350011,China;Department of Cardiology,Beijing Anzhen Hospital,Capital Medical University,Beijing Institute of Heart,Lung,Blood Vessel Diseases,Beijing 100029,China;Department of Cardiology,Shanghai Jiaotong University School of Medicine,Shanghai Children′s Medical Center,Shanghai 200127,China;Department of Pediatrics,Fujian Provincial Maternity and Children′s Hospital,Fuzhou 350001,China;Department of Cardiology,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200092,China)

机构地区：[1]福建省儿童医院心内科,福州350011 [2]首都医科大学附属北京安贞医院心内科北京市心肺血管病研究所,北京100029 [3]上海交通大学医学院附属上海儿童医学中心心内科,上海200127 [4]福建省妇幼保健院儿科,福州350001 [5]上海交通大学医学院附属新华医院心内科,上海200092

出　　处：《中华心血管病杂志》2024年第2期172-179,共8页Chinese Journal of Cardiology

基　　金：福建省自然科学基金资助项目(2022J011072);福建省卫生健康委员会科技计划项目(2022CXB011)。

摘　　要：目的分析高尿酸血症-肺动脉高压-肾衰竭-碱中毒综合征(HUPRAS)的SARS2致病基因特定位点的致病性。方法选取2022年3月9日就诊于福建省儿童医院的HUPRAS患儿1例,对患儿进行临床和实验室检查,抽取患儿及其父母外周血进行全外显子基因变异检测,并对所筛选的变异进行Sanger测序验证及生物信息学分析。结果患儿男,6个月,其SARS2等位基因分别携带父系遗传的c.1205G>A/p.Arg402His变异和母系遗传的c.680G>A/p.Arg227Gln变异,其中c.680G>A既往未被报道。这两个变异人群频率极低,致病性软件预测其有害。Arg402和Arg227均进化高度保守,突变导致其编码的丝氨酰tRNA合成酶的氢键结构及疏水性均产生了变化,提示这两个变异能够解释患儿HUPRAS表型。结论SARS2基因的c.1205G>A/p.Arg402His和c.680G>A/p.Arg227Gln复合杂合变异可能导致HUPRAS。Objective To explore the clinical manifestations and genotype of an infant with hyperuricemia,pulmonary hypertension,renal failure in infancy,and alkalosis syndrome(HUPRAS).Methods Clinical data of the patient were collected.Peripheral blood samples from the patient and his parents were acquainted for whole exome sequencing.The filtrated variants were verified by Sanger sequencing.The pathogenicity of the variants was predicted by bioinformatic tools.Results The patient is a male infant of 6 months old,carrying two missense variants in the SARS2 allele:a paternal inherited c.1205G>A(p.Arg402His)and a maternal inherited c.680G>A(p.Arg227Gln).The two variants were in extremely low population frequencies.The pathogenetic prediction tools categorized them as deleterious.Arg402 and Arg227 were highly conserved in evolution.The variants led to changes in the hydrogen bonds and hydrophobicity of seryl-tRNA synthetase encoded by SARS2.Conclusions c.1205G>A(p.Arg402His)and c.680G>A(p.Arg227Gln)are the possible causative variants of the HUPRA syndrome.

关 键 词：线粒体疾病 SARS2基因 HUPRA综合征 错义突变 

分 类 号：R725[医药卫生—儿科]