Prenatal exome sequencing in fetuses with congenital heart defects
Prenatal exome sequencing in fetuses with congenital heart defects
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先天性心脏病胎儿的产前外显子组测序
DOI：
10.1111/cge.13774
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发表时间：
2020-06-09
影响因子：
3.5
通讯作者：
Liao, Can
中科院分区：
文献类型：
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作者：
Li, Ru;Fu, Fang;Liao, Can
先天性心脏病（CHD）的基因诊断是具有挑战性的，因为遗传和表型的异质性。本研究的目的是在一个大的队列中评价全外显子组测序（WES）在CHD产前诊断中的临床价值。在260例核型和染色体微阵列分析结果为阴性的CHD胎儿中进行了基于Trio的WES。在整个队列中，WES的诊断率为10%（26/260）。心脏横纹肌瘤、复杂心脏瓣膜病、间隔缺损、圆锥动脉干缺损的诊断率分别为60%、16.7%、14.0%、9.9%。简单和复杂CHD组的诊断率（9.9% vs 16.7%）与非孤立和孤立CHD组（15.7% vs 7.9%）之间无显著差异。软标记物CHD、胎儿生长受限CHD和其他结构异常CHD（综合征型CHD）的诊断率分别为0（0/13）、50%（1/2）和18.2%（10/55）。在16例（6.2%）胎儿中检测到意义不明的变异，在7例（2.7%）病例中检测到继发性结果。在14个候选基因的变异进行了鉴定。我们的研究表明，在常规检查后，基于三重的WES在CHD的产前诊断中的诊断率增加，但没有预期的高。
The genetic diagnosis of congenital heart defects (CHDs) is challenging because of genetic and phenotypic heterogeneity. The aim of our study was to evaluate the clinical value of whole exome sequencing (WES) in the prenatal diagnosis of CHDs in a large cohort. Trio‐based WES was performed in 260 fetuses with CHDs negative for karyotype and chromosome microarray analysis results. WES produced a diagnostic yield of 10% (26/260) in the entire cohort. Relative high diagnostic rate was observed in cases with cardiac rhabdomyoma (60%), complex CHDs (16.7%), septal defect (14.0%), and conotruncal defect (9.9%). There was no significant difference between the diagnostic yields in simple and complex CHDs groups (9.9% vs 16.7%), and in non‐isolated and isolated CHDs groups (15.7% vs 7.9%). The diagnostic yields in cases with CHDs with soft markers, CHDs with fetal growth restriction, and CHDs with other structural anomalies (syndromic CHDs) were 0 (0/13), 50% (1/2) and 18.2% (10/55), respectively. Variants of unknown significance were detected in 16 (6.2%) fetuses, and secondary findings in 7 (2.7%) cases. Variants in 14 candidate genes were identified. Our study demonstrates an incremental diagnostic yield by trio‐based WES in the prenatal diagnosis of CHDs after routine tests, not as high as expected.