Objectives This study aimed to describe the genetic and clinical characteristics of paediatric cardiomyopathy in a cohort of Chinese patients.Methods We retrospectively reviewed the clinical history and mutation spectrum of 75 unrelated Chinese paediatric patients who were diagnosed with cardiomyopathy and referred to our hospital between January 2016 and December 2022.Results Seventy-five children with cardiomyopathy were enrolled, including 32 (42.7%) boys and 43 (57.3%) girls. Dilated cardiomyopathy was the most prevalent cardiomyopathy (61.3%) in the patients, followed by hypertrophic cardiomyopathy (17.3%), ventricular non-compaction (14.7%), restrictive cardiomyopathy (5.3%) and arrhythmogenic right ventricular cardiomyopathy (1.3%). Whole-exome sequencing and targeted next-generation sequencing identified 34 pathogenic/likely pathogenic variants and 1 copy number variant in 14 genes related to cardiomyopathy in 30 children, accounting for 40% of all patients. TNNC1 p.Asp65Asn and MYH7 p.Glu500Lys have not been reported previously. The follow-up time ranged from 2 months to 6 years. Twenty-two children died (mortality rate 29%).Conclusions Comprehensive genetic testing was associated with a 40% yield of causal genetic mutations in Chinese cardiomyopathy cases. We found diversity in the mutation profile in different patients, which suggests that the mutational background of cardiomyopathy in China is heterogeneous, and the findings may be helpful to those counselling patients and families.

目的:探讨微小RNA-19a-3p(miR-19a-3p)/细胞因子信号抑制物3(SOCS3)信号轴在川崎病(KD)病理发展过程中的调控机制.方法:采集我院川崎病患儿、川崎病治疗后患儿血清,采用实时荧光定量PCR(RT-qPCR)及蛋白质印迹(Western Blot)法检测miR-19a-3p、SOCS3 mRNA及蛋白表达变化.小鼠腹腔注射白色念珠菌水溶物(CAWS)建立川崎病模型,分为正常对照组、模型组、si-miR-19a-3p组、ad-SOCS3组、si-NC组、ad-NC组,每组10只.取小鼠冠状动脉组织,采用酶联免疫吸附实验(ELISA)检测肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、诱导型一氧化氮合酶(iNOS)、血管内皮素(ET)水平;苏木素-伊红(HE)染色法观察冠状动脉病理变化;免疫组化法检测SOCS3阳性表达水平;RT-qPCR及Western Blot法检测miR-19a-3p、SOCS3 mRNA及蛋白表达变化;Western Blot法检测Janus酪氨酸蛋白激酶2(JAK2)、信号转导和转录激活因子3(STAT3)、磷酸化STAT3(p-STAT3)、核转录因子-κB(NF-κB)、磷酸化NF-κB(p-NF-κB)蛋白表达水平.取人冠状动脉内皮细胞(HCAEC),用川崎病患儿血清培养HCAEC以模拟体外川崎病模型,并分为正常对照组、川崎病组、si-miR-19a-3p组、si-SOCS3组、si-miR-19a-3p+si-SOCS3组、si-NC-1组、si-NC-2组;ELISA法检测细胞上清液炎性因子TNF-α、IL-1β水平;流式细胞术检测细胞凋亡率;管腔形成试验检测管腔形成情况;RT-qPCR法及Western Blot法检测miR-19a-3p、SOCS3 mRNA及蛋白表达变化.结果:川崎病患儿血清中miR-19a-3p表达升高,SOCS3 mRNA及蛋白表达降低(P<0.05);随着川崎病患儿康复,miR-19a-3p、SOCS3 mRNA及蛋白表达均趋于正常.沉默miR-19a-3p及上调SOCS3表达后,川崎病小鼠死亡减少,冠状动脉血管损伤缓解,SOCS3介导的炎性通路相关蛋白表达降低(P<0.05).下调SOCS3表达可逆转miR-19a-3p沉默发挥抑制HCAEC凋亡、管腔形成、炎性因子分泌等作用(P<0.05).结论:miR-19a-3p高表达、SOCS3低表达可能参与川崎病血管炎性损伤过程,沉默miR-19a-3p可靶向上调SOCS3表达,抑制炎症反应,减轻川崎病冠状动脉血管损伤.

OBJECTIVE:To explore the clinical and genetic characteristics of five children with Catecholaminergic polymorphic ventricular tachycardia (CPVT).METHODS:Five children with clinical manifestations consistent with CPVT admitted to the Department of Cardiology of Children's Hospital Affiliated to Zhengzhou University from November 2019 to November 2021 were selected as the study subjects. Their clinical data were collected. Potential variants were detected by whole exome sequencing, and Sanger sequencing was used to verify the candidate variants. All patients were treated with β-blocker propranolol and followed up.RESULTS:All patients had developed the disease during exercise and presented with syncope as the initial clinical manifestation. Electrocardiogram showed sinus bradycardia. The first onset age of the 5 patients were (10.4 ± 2.19) years, and the time of delayed diagnosis was (1.6 ± 2.19) years. All of the children were found to harbor de novo heterozygous missense variants of the RYR2 gene, including c.6916G>A (p.V2306I), c.527G>C (p.R176P), c.12271G>A (p.A4091T), c.506G>T (p.R169L) and c.6817G>A (p.G2273R). Among these, c.527G>C (p.R176P) and c.6817G>A (p.G2273R) were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.527G>C (p.R176P) was classified as a pathogenic variant (PS2+PM1+PM2_Supporting+PM5+PP3+PP4), and the c.6817G>A (p.G2273R) was classified as a likely pathogenic variant (PS2+PM2_Supporting+PP3+PP4). The symptoms of all children were significantly improved with the propranolol treatment, and none has developed syncope during the follow up.CONCLUSION:Discovery of the c.527G>C (p.R176P) and c.6817G>A (p.G2273R) variants has expanded the mutational spectrum of the RYR2 gene. Genetic testing of CPVT patients can clarify the cause of the disease and provide a reference for their genetic counseling.

目的 探讨川崎病(KD)患儿血浆微小核糖核酸-223(miR-223)、FGD5-AS1的表达水平及临床意义.方法 选取收治的KD患儿75例作为KD组,选取同期参加体检的健康儿童60例作为健康对照组,感染发热患儿60例作为发热对照组.根据冠状动脉Z值将KD组患儿分为无冠状动脉损伤组59例和冠状动脉损伤组16例.采用实时荧光定量PCR检测研究对象血浆miR-223、FGD5-AS1表达水平;采用Pearson检验分析KD患儿血浆FGD5-AS1与miR-223表达水平的相关性;使用ROC曲线分析FGD5-AS1、miR-223对KD患儿冠状动脉损伤的诊断价值.结果 KD组、发热对照组患儿血小板计数(PLT)、血沉(ESR)及血浆miR-223、白细胞介素-6(IL-6)、氨基末端脑钠肽前体(NT-proBNP)表达水平均明显高于健康对照组儿童,FGD5-AS1表达水平明显低于健康对照组儿童(P<0.05).KD组患儿PLT、ESR及血浆miR-223、IL-6、NT-proBNP表达水平均明显高于发热对照组患儿,FGD5-AS1表达水平明显低于发热对照组患儿(P<0.05).治疗后KD患儿血浆miR-223表达水平明显降低,FGD5-AS1表达水平明显升高(P<0.05).KD患儿血浆miR-223与FGD5-AS1表达水平呈负相关(P<0.05);miR-223表达水平与血浆IL-6、NT-proBNP表达水平均呈正相关(P<0.05),FGD5-AS1表达水平与血浆IL-6、NT-proBNP表达水平均呈负相关(P<0.05).冠状动脉损伤组患儿PLT、ESR及血浆miR-223、IL-6、NT-proBNP表达水平均明显高于无冠状动脉损伤组患儿,FGD5-AS1表达水平明显低于无冠状动脉损伤组患儿(P<0.05).血浆FGD5-AS1、miR-223水平联合检测对KD患儿冠状动脉损伤诊断的曲线下面积为0.907(95％CI:0.845～0.969),优于二者单独检测.结论 KD患儿血浆FGD5-AS1表达水平明显降低、miR-223表达水平明显升高,二者间可能存在相互作用参与KD进展,可作为评估冠状动脉损伤发生的有效指标.

目的:研究血清脑利尿钠肽(BNP)、血清可溶性肿瘤坏死因子样弱凋亡诱导因子(sTWEAK)水平与扩张型心肌病(DCM)患儿并发心室重构、急性失代偿性心力衰竭(ADHF)的相关性.方法:回顾性选取2018年10月至2020年10月期间河南省儿童医院收治的45例DCM并发心室重构患儿作为本研究的心室重构组;选取同期收治的46例DCM并发ADHF患儿为ADHF组;再选取同期收治的DCM未发生心室重构、ADHF的45例患儿为DCM组.三组患儿均测定血清BNP、sTWEAK水平,ADHF组和DCM组测定左室射血分数(LVEF),心室重构组和DCM组测定左心室舒张末期内径(LVEDD),比较三组患儿血清BNP、sTWEAK水平,分析血清BNP、sTWEAK与LVEDD、LVEF的相关性.并使用受试者工作特征曲线(ROC)分析血清BNP、sTWEAK水平联合诊断DCM并发心室重构、DCM并发ADHF的诊断价值.结果:心室重构组患儿的血清BNP水平明显高于DCM组、ADHF组,sTWEAK水平明显低于DCM组、ADHF组;ADHF组患儿血清BNP水平明显高于DCM组,sTWEAK水平明显低于DCM组,差异均具有统计学意义(P＜0.05).经Pearson相关性分析,LVEF与血清BNP负相关(r=-0.835,P＜0.001),与血清 sTWEAK 正相关(r=0.679,P＜0.001);LVEDD 与血清 BNP 正相关(r=0.899,P＜0.001),与血清sTWEAK负相关(r=-0.712,P＜0.001).ROC曲线分析结果显示,血清BNP、sTWEAK联合诊断DCM并发ADHF以及DCM并发心室重构的效能均高于两者单独诊断.结论:血清BNP、sTWEAK水平与DCM患儿并发心室重构或ADHF存在相关性,二者联合诊断对DCM患儿并发心室重构或ADHF具有较高诊断价值.

目的 观察病毒性心肌炎(VMC)病儿血浆外泌体微小RNA(miR)-148a的水平并分析其意义.方法 选择2017年9月至2019年6月郑州大学附属儿童医院收治的VMC病儿112例纳入研究组,另选取同期门诊健康体检正常儿童112例为对照组,实时荧光定量PCR(RT-qPCR)检测血浆外泌体miR-148a水平,酶联免疫吸附测定(ELISA)检测血浆外泌体心肌肌钙蛋白I(cTnI),采用自动化生化仪检测血浆外泌体肌酸激酶同工酶(CK-MB)水平、超敏C反应蛋白(hs-CRP)水平.采用Pearson相关性分析检验VMC病儿血浆外泌体miR-148a与cTnI、CK-MB、hs-CRP水平的相关性.绘制受试者工作特征曲线(ROC)分析血浆外泌体miR-148a对VMC的诊断价值.结果 血浆外泌体在透射电镜下呈大小不等、直径约100 nm典型圆形或椭圆形囊泡结构.与对照组比较,研究组血浆外泌体miR-148a水平[(1.01±0.12)比(5.34±1.06)]、血浆cTnI、CK-MB、hs-CRP水平均增加(均P<0.001).VMC病儿血浆外泌体miR-148a与血浆cTnI、CK-MB、hs-CRP水平均呈正相关(r=0.62、0.64、0.49,均P<0.001).血浆外泌体miR-148a及血浆cTnI、CK-MB、hs-CRP诊断早期VMC的曲线下面积(AUC)分别为0.94、0.94、0.83、0.86,截断值分别为1.87、0.19μg/L、56.45 U/L、2.06 mg/L,灵敏度分别为94.60％、92.90％、84.80％、83.90％,特异度分别为92.90％、94.60％、83.90％、83.90％.血浆外泌体miR-148a与血浆cTnI诊断早期VMC的效能一致,均优于血浆CK-MB、hs-CRP.结论 VMC病儿血浆外泌体miR-148a水平上调,可能对VMC有一定诊断价值.

目的:深入探讨脑利钠肽和红细胞分布宽度在婴儿川崎病冠状动脉病变中的应用价值,预防和减少冠状动脉病变,从而改善川崎病患儿的预后.方法:回顾性分析2018年1月—2019年12月在郑州大学附属儿童医院收治的已经出院确诊为婴儿川崎病的113例患儿的临床资料,并对其进行总结分析.结果:CAL组WBC、RDW和BNP水平显著升高,差异有统计学意义.WBC、RDW和BNP水平增高是CAL的独立危险因素.RDW≥13.4％预测川崎病合并冠脉病变的灵敏度为74.4％,特异度为75.7％,ROC曲线下的面积为0.757.BNP≥325 pg/mL预测川崎病合并冠脉病变的灵敏度为90.7％,特异度为74.3％,ROC曲线下的面积为0.862.结论:BNP、RDW升高可作为预测川崎病患儿合并CAL的危险因素.

目前川崎病的病因及发病机制尚不清楚,但近年来,大量流行病学资料显示发现KD的发病具有一定的遗传背景.现就与川崎病相关的FCGR2A基因多态性、CD40及配体CD40L基因多态性、FAM-BLK基因多态性、ITPKC基因多态性、CASP3基因多态性和HLA基因多态性的研究进展作一综述.