超声心动图评估胎儿先天性心脏病拷贝数变异的作用

Role of echocardiography in assessing copy number variation in fetal congenital heart disease

目的探讨超声心动图对先天性心脏病(congenital heart disease,CHD)胎儿拷贝数变异(copy number variation,CNV)的应用价值。方法回顾性选取2019年1月至2022年8月在泉州市妇幼保健院儿童医院行超声心动图提示胎儿CHD并接受介入性产前诊断的447例单胎孕妇作为研究对象,这些孕妇均行染色体核型分析及染色体微阵列分析(chormosome microarray analysis,CMA)检测。分析CMA和核型分析2种方法的染色体异常检出差异,以及不同心脏表型(是否合并心外结构畸形、心脏结构畸形的类型和数量)的CHD之间的致病性拷贝数变异(pathogenic copy number variation,pCNV)检出率差异。采用χ^(2)检验进行统计学分析。结果CMA较染色体核型分析有更高的胎儿染色体异常检出率[10.5%(47/447)与20.6%(92/447),χ^(2)=161.56,Ρ<0.001]。不同心脏表型中,CHD伴心外结构畸形组pCNV检出率高于单纯CHD组[11.4%(45/394)与32.1%(17/53),χ^(2)=16.68,Ρ<0.001]。对于不同心脏结构畸形,间隔缺损畸形、圆锥动脉干畸形、左心系统畸形pCNV检出率均分别高于其他心脏畸形[18.4%(29/158)、25.9%(7/27)、25.0%(7/28)与7.6%(16/210),χ^(2)值分别为9.15、9.68和8.55,P值均<0.05]。CMA检出与CHD相关的pCNV包括22q11.2缺失/重复8例、4p16.3缺失2例、11q23.3微重复2例、1q21.1微缺失/微重复2例、4q28.3微重复1例、10p15.3微缺失1例等。结论CMA技术能够提高CHD胎儿pCNV的检出率,超声心动图可以指导有针对性的CMA筛查,有助于产前CHD的遗传学评估。

ObjectiveThis study examines the application of echocardiography in the prenatal diagnosis of copy number variation(CNV)associated with fetal congenital heart disease(CHD).MethodsA retrospective analysis was conducted on 447 singleton pregnancies from Quanzhou Maternal and Child Care Hospital(Quanzhou Children's Hospital)from January 2019 to August 2022.These individuals underwent echocardiographic assessments suggestive of fetal CHD and subsequently received invasive prenatal diagnoses.Comprehensive karyotype analysis and chromosome microarray analysis(CMA)were performed for each case.The discrepancies in the chromosomal abnormality detection were analyzed between the results produced by CMA and karyotype analysis.Furthermore,differences in the detection of pathogenic copy number variation(pCNV)between the two methods in CHD cases with diverse cardiac phenotypes,including the presence or absence of extracardiac structural malformations,the type,and quantity of cardiac structural anomalies,were explored.Statistical analysis was conducted using the Chi-square test.ResultsCompared with conventional karyotype analysis,CMA demonstrated a higher detection rate of fetal chromosomal abnormalities[10.5%(47/447)vs.20.6%(92/447),χ^(2)=161.56,P<0.001].In terms of distinct cardiac phenotypes,CHD cases with extracardiac structural anomalies displayed an escalated pCNV detection rate in comparison to isolated CHD cases[11.4%(45/394)vs.32.1%(17/53),χ^(2)=16.68,P<0.001].Within the cardiac structural anomaly subgroups,increased pCNV detection rates were observed in the septal defect subgroup,conotruncal malformation subgroup,and left ventricular malformation subgroup[18.4%(29/158),25.9%(7/27),and 25.0%(7/28)vs.7.6%(16/210);χ^(2)=9.15,9.68,and 8.55,respectively,all P<0.05].The CMA-identified pCNV correlated with CHD included 22q11.2 deletions/duplications in eight cases,4p16.3 deletions in two cases,11q23.3 microduplications in two cases,1q21.1 microdeletions/microduplications in two cases,4q28.3 microduplications in one case,and 10p15.3 microdeletions in one case.ConclusionsCMA technology exhibited an enhanced ability to detect pCNV in fetuses with CHD.Echocardiography can guide targeted CMA screening,thereby facilitating prenatal genetic assessment of CHD.