三例心脏横纹肌瘤胎儿的基因诊断  

Genetic analysis of three fetusesaffected with cardiac rhabdomyomas

作　　者：侯瑞 吕远[1] 李闯 廖姗姗[1] 张琰[2] 李岭 刘彩霞[1] Hou Rui;Lyu Yuan;Li Chuang;Liao Shanshan;Zhang Yan;Li-Ling Jesse;Liu Caixia(Department of Gynecology&Obstetrics,Shengjing Hospital Affiliated to China Medical University,Key Laboratory of Maternal-Fetal Medicine of Liaoning Province,Shenyang,Liaoning 110004,China;Obstetrics Outpatient Clinic,Shenyang Woman’s and Children’s Hospital,Shenyang,Liaoning 110011,China)

机构地区：[1]中国医科大学附属盛京医院妇产科、辽宁省母胎医学重点实验室,沈阳110004 [2]沈阳市妇婴医院产科门诊,110011 [3]四川大学华西医院生物治疗国家重点实验室,成才610041

出　　处：《中华医学遗传学杂志》2020年第6期629-632,共4页Chinese Journal of Medical Genetics

基　　金：辽宁省产科疾病临床医学研究中心及协同网络建设项目(2016007014);国家自然科学基金(81701462);常见高危胎儿诊治技术标准及规范的建立与优化(201402006);国家重点研发项目(2016YFC1000408)。

摘　　要：目的探讨超声心动图联合基因检测对胎儿心脏横纹肌瘤的诊断意义。方法收集2018年3月至2019年3月于中国医科大学附属盛京医院经超声诊断为心脏横纹肌瘤的3例胎儿的临床资料及引产后胎儿组织。应用高通量测序技术对胎儿样本进行全外显子测序,应用Sanger测序技术对筛查到的可疑变异位点进行验证。检索胎儿心脏横纹肌瘤相关文献,总结胎儿超声心动图特征及基因诊断结果。结果3个家系胎儿超声心动图结果均提示心室内多发高回声团,确诊为心脏横纹肌瘤。基因检测结果提示家系1胎儿携带TSC1基因c.740G>A(p.W247*)杂合变异,家系2胎儿携带TSC2基因c.3352C>T(p.Q1118*)杂合变异,家系3胎儿携带TSC1基因c.1579C>T(p.Q527*)杂合变异,3个家系中胎儿父母均未携带相应变异。统计分析109例资料较为完整的心脏横纹肌瘤胎儿,其中79例胎儿心脏横纹肌瘤为多发性,89例横纹肌瘤位于心室及室间隔上,完善基因诊断的94例胎儿中74例携带有TSC1或TSC2基因变异。结论胎儿心脏横纹肌瘤常表现为心室内多发性高回声团,且多数为结节性硬化症的胎儿期表现,建议进一步完善产前基因诊断。Objective To reported on echocardiographic finding and genetic testing of three fetuses with cardiac rhabdomyoma.Methods Clinical data of the three fetuses was collected.High-throughput sequencing was carried out to analyze the whole exomes of the three fetuses.Suspected variants were confirmed by Sanger sequencing.Results Multiple hyperechoic masses were found in both ventricles of the three fetuses,suggesting the presence of fetal cardiac rhabdomyoma.Genetic testing revealed that fetus 1 carried a heterozygous c.740G>A(p.W247*)variant of the TSC1 gene,fetus 2 carried a previously known heterozygous c.3352C>T(p.Q1118*)variant of the TSC2 gene.Fetus 3 carried a previously known heterozygous c.1579C>T(p.Q527*)variant of the TSC1 gene.None of their parents carried the same variant.Literature review has identified 109 fetuses with relatively complete data.Cardiac rhabdomyomas in ventricles and ventricular septum was reported in 89,and multiple cardiac rhabdomyoma was reported in 79.Out of the 94 cases who underwent genetic testing,74 have carried variants of the TSC1 or TSC2 genes.Conclusion Fetal cardiac rhabdomyoma may present as multiple hyperechoic intraventricular masses.Most of them are associated with other manifestation of tuberous sclerosis.Such cases may warrant prenatal genetic testing.

关 键 词：心脏横纹肌瘤 胎儿超声心动图 结节性硬化症 TSC1/TSC2基因变异 

分 类 号：R714.5[医药卫生—妇产科学] R440[医药卫生—临床医学]