肾病综合征合并心律失常患儿1例临床特点及基因变异分析  

Clinical characteristics and genetic variation analysis of a child with nephrotic syndrome complicated with arrhythmia

作　　者：雷凤英[1] 刘雪婷 陈秀萍[1] 黄韦芳[1] 覃远汉[1] Lei Fengying;Liu Xueting;Chen Xiuping;Huang Weifang;Qin Yuanhan(Department of Pediatrics,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院儿科,南宁530021

出　　处：《广西医科大学学报》2023年第9期1535-1539,共5页Journal of Guangxi Medical University

基　　金：广西自然科学青年科学基金资助项目(No.2018GXNSFBA050014);广西儿科疾病临床医学研究中心资助项目(No.桂科AD22035219)。

摘　　要：目的:总结分析1例激素耐药性肾病综合征(SRNS)合并心律失常(房室传导阻滞、室性早搏)患儿的临床特征和基因变异特点,提高临床医师对该病的认识。方法:收集1例临床确诊为SRNS、房室传导阻滞和室性早搏患儿的临床资料,复习相关文献,分析其基因变异与临床特征的联系。结果:女性患儿,8岁2个月,临床表现为大量蛋白尿、低蛋白血症、高胆固醇血症、肾小球源性血尿、高血压,肾脏病理为局灶节段性肾小球硬化(FSGS),予泼尼松和他克莫司治疗无效,符合SRNS的诊断,同时合并房室传导阻滞、室性早搏等心律失常表现。高精度临床外显子检测发现,患儿Podocin编码基因(NPHS2)存在复合杂合突变c.412C>T(p.R138*)和c.8710T(p.R291W);Sanger测序验证提示c.8710T(p.R291W)来源于母亲(杂合状态),c.412C>T(p.R138*)为新发变异(杂合状态)。检出心脏钠通道孔隙形成α亚基基因(SCN5A)存在杂合变异c.4018G>A(p.V1340I),Sanger测序验证提示该变异来源于父亲(杂合状态)。结论:NPHS2基因突变是导致本例患儿发生SRNS的原因,但该基因突变所致肾病综合征通常无肾外表现,患儿出现心律失常可能与SCN5A基因杂合突变有关。Objective:To summarize and analyze the clinical characteristics and genetic variations of a child with steroid-resistant nephrotic syndrome(SRNS)complicated with arrhythmia(atrioventricular block and ventricular premature beats),so as to improve clinicians’understanding of the disease.Methods:The clinical data of a child with clinically confirmed SRNS,atrioventricular block,and ventricular premature beats were collected,and the relevant literature was reviewed to analyze the relationship between genetic variation and clinical characteristics.Results:The patient was a female,8 years and 2 months old,with clinical manifestations of massive proteinuria,hypoproteinemia,hypercholesterolemia,glomerulogenic hematuria,and hypertension.The renal pathology showed focal segmental glomerulosclerosis(FSGS).Prednisone and tacrolimus were ineffective,which was consistent with the diagnosis of SRNS.At the same time,it was combined with arrhythmia such as atrioventricular block and ventricular premature beats.High-precision clinical exome detection revealed that there were compound heterozygous mutations c.412C>T(p.R138*)and c.8710T(p.R291W)in the Podocin coding gene(NPHS2)of the child;Sanger sequencing validation suggested that c.8710T(p.R291W)originated from the mother(heterozygous state),and c.412C>T(p.R138*)was a newly discovered mutation(heterozy-gous state).A heterozygous mutation c.4018G>A(p.V1340I)in the heart sodium channel pore-formingαsubunit gene(SCN5A)was detected in the child,and Sanger sequencing showed that the mutation originated from the father(heterozygous state).Conclusion:The mutation in the NPHS2 gene is the cause of SRNS in this case,but nephrotic syndrome caused by this gene mutation usually has no extrarenal manifestations,and the occurrence of arrhythmia in the child may be associated with a heterozygous mutation in the SCN5A gene.

关 键 词：激素耐药性肾病综合征 心律失常 NHPS2 SCN5A 局灶节段性肾小球硬化症 

分 类 号：R726.9[医药卫生—儿科]