Congenital cardiovascular malformations (CVMs) due to genomic mutations bring a greater risk of morbidity and comorbidity and increase the risks related to heart surgery. However, reports on CVMs induced by genomic mutations based on actual clinical data are still limited. In this study, 181 fetuses were screened by fetal echocardiography for prenatal diagnosis of congenital heart disease, including 146 cases without ultrasound extracardiac findings (Group A) and 35 cases with ultrasound extracardiac findings (Group B). All cases were analyzed by clinical data, karyotyping, and low-depth whole-genome sequencing. The rates of chromosomal abnormalities in Groups A and B were 4.8% (7/146) and 37.1% (13/35), respectively. There was a significant difference in the incidence of chromosomal abnormalities between Groups A and B (p #x3c; 0.001). In Group A, CNV-seq identified copy number variations (CNVs) in an additional 9.6% (14/146) of cases with normal karyotypes, including 7 pathogenic CNVs and 7 variations of uncertain clinical significance. In Group B, one pathogenic CNV was identified in a case with normal karyotype. Chromosomal abnormality is one of the most common causes of CVM with extracardiac defects. Low-depth whole-genome sequencing could effectively become a first approach for CNV diagnosis in fetuses with CVMs.
Cytogenet Genome Res

中文翻译：

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先天性心血管畸形胎儿低深度全基因组测序的拷贝数变异分析

基因组突变导致的先天性心血管畸形（CVM）带来更大的发病和合并症风险，并增加了与心脏手术有关的风险。然而，基于实际临床数据的由基因组突变诱导的CVM的报道仍然有限。在这项研究中，通过胎儿超声心动图筛查了181例胎儿，用于先天性心脏病的产前诊断，包括146例无超声心外膜表现的患者（A组）和35例有超声心外膜表现的患者（B组）。所有病例均通过临床数据，核型分析和低深度全基因组测序进行了分析。A组和B组的染色体异常率分别为4.8％（7/146）和37.1％（13/35）。A组和B组之间染色体异常的发生率有显着差异（p＃x3c; 0.001）。在A组中，CNV-seq在正常核型的另外9.6％（14/146）病例中识别出拷贝数变异（CNV），包括7个病原体CNV和7个临床意义不确定的变异。在B组中，在核型正常的情况下鉴定出一种病原性CNV。染色体异常是伴有心外膜缺损的CVM的最常见原因之一。低深度全基因组测序可以有效地成为具有CVM的胎儿CNV诊断的第一种方法。
细胞遗传学基因组研究