Wang Xuezhen, Sha Jing, Han Yu, Pang Min, Liu Min, Liu Mengna, Zhang Bei, Zhai Jingfang
Department of Prenatal Diagnosis Medical Center, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Jiefang South Road No.199, Xuzhou, 221009, Jiangsu, China.
Graduate School of Bengbu Medical University, Donghai Avenue No.2600, Bengbu, 233000, Anhui, China.
Mol Cytogenet. 2024 May 13;17(1):12. doi: 10.1186/s13039-024-00681-5.
Both copy number variant-sequencing (CNV-seq) and karyotype analysis have been used as powerful tools in the genetic aetiology of fetuses with congenital heart diseases (CHD). However, CNV-seq brings clinicians more confusions to interpret the detection results related to CHD with or without extracardiac abnormalities. Hence, we conducted this study to investigate the clinical value of CNV-seq in fetuses with CHD.
A total of 167 patients with fetal CHD including 36 single CHD (sCHD), 41 compound CHD (cCHD) and 90 non-isolated CHD (niCHD) were recruited into the study. 28 cases (16.77%, 28/167) were revealed with chromosomal abnormalities at the level of karyotype. The pathogenic detection rate (DR) of CNV-seq (23.17%, 19/82) was higher than that of karyotyping (15.85%, 13/82) in 82 cases by CNV-seq and karyotyping simultaneously. The DR of pathogenic copy number variations (PCNVs) (31.43%) was higher in niCHD subgroup than that in sCHD and cCHD (9.52% and 23.08%). Conotruncal defect (CTD) was one of the most common heart malformations with the highest DR of PCNVs (50%) in 7 categories of CHD. In terms of all the pregnancy outcomes, 67 (40.12%) cases were terminated and 100 (59.88%) cases were live neonates. Only two among 34 cases with a pathogenic genetic result chose to continue the pregnancy.
CNV-seq combined with karyotyping is a reliable and accurate prenatal technique for identifying pathogenic chromosomal abnormalities associated with fetal CHD with or without extracardiac abnormalities, which can assist clinicians to perform detailed genetic counselling with regard to the etiology and related outcomes of CHD.
拷贝数变异测序（CNV-seq）和核型分析均已成为先天性心脏病（CHD）胎儿遗传病因学研究的有力工具。然而，CNV-seq在解读伴有或不伴有心外异常的CHD相关检测结果时给临床医生带来了更多困惑。因此，我们开展了本研究以探讨CNV-seq在CHD胎儿中的临床价值。
本研究共纳入167例胎儿CHD患者，其中包括36例单纯CHD（sCHD）、41例复合CHD（cCHD）和90例非孤立性CHD（niCHD）。核型水平显示28例（16.77%，28/167）存在染色体异常。在82例同时进行CNV-seq和核型分析的病例中，CNV-seq的致病检出率（DR）（23.17%，19/82）高于核型分析（15.85%，13/82）。致病拷贝数变异（PCNVs）在niCHD亚组中的DR（31.43%）高于sCHD和cCHD亚组（9.52%和23.08%）。圆锥动脉干缺损（CTD）是最常见的心脏畸形之一，在7类CHD中PCNVs的DR最高（50%）。就所有妊娠结局而言，67例（40.12%）终止妊娠，100例（59.88%）为活产新生儿。在34例有致病基因结果的病例中，只有2例选择继续妊娠。
CNV-seq联合核型分析是一种可靠且准确的产前技术，可用于识别伴有或不伴有心外异常的胎儿CHD相关致病染色体异常，有助于临床医生就CHD的病因及相关结局进行详细的遗传咨询。
