期刊
ULTRASOUND IN OBSTETRICS & GYNECOLOGY
卷 52, 期 2, 页码 205-211出版社
WILEY
DOI: 10.1002/uog.19042
关键词
congenital heart defects; pathogenic variant; prenatal diagnosis; targeted next-generation sequencing
资金
- National Natural Science Foundation of China [81 602 300, 81 770 236, 81 701 427, 81 671 475, 81 500 244]
- Natural Science Foundation of Jiangsu Province [BK20160139]
- Project on Social Development of Jiangsu Province [BE2015614]
- Foundation of Jiangsu Provincial Department of Health [H201343, F201314]
- Project on Maternal and Child Health Talents of Jiangsu Province [FRC201791]
Objectives To assess the value of targeted next-generation sequencing (NGS) in prenatal diagnosis of congenital heart defects (CHD) and to investigate the genetic etiology of prenatal CHD. Methods Forty-four fetuses with CHD, normalmolecular karyotype and negative chromosomal microarray results underwent targeted NGS. Fetal genomic DNA was extracted directly from amniotic fluid cells in each prenatal case. A customized targeted-NGS panel of 77 CHD-associated genes was designed to detect variants in the coding regions and the splicing sites of these genes. The detected variants were classified as pathogenic, likely pathogenic, of uncertain significance, likely benign or benign, following the guidelines recommended by the American College of Medical Genetics and Genomics. Results The detection rates of targeted NGS for pathogenic and likely pathogenic variations were 13.6% (6/44) and 2.3% (1/44), respectively. The turnaround time of the test was 3weeks. The six pathogenic variations were identified on the genes CHD7 (CHARGE syndrome), CITED2 (tetralogy of Fallot, ventricular septal defect and atrial septal defect), ZFPM2 (tetralogy of Fallot), MYH6 (atrial septal defect, familial isolated dilated cardiomyopathy) and, in two cases, KMT2D (Kabuki syndrome). The likely pathogenic variation was detected on JAG1, which is associated with tetralogy of Fallot and Alagille syndrome. Sanger sequencing in the fetuses and their parents indicated that all seven mutations were de novo. Variations of uncertain significance were detected in 79.5% of cases. Conclusions Targeted NGS in fetuses with isolated and non-isolated CHD achieved a high diagnostic yield in our cohort, with an acceptable turnaround time for the prenatal setting. Our results have important implications for clinical management and genetic counseling. Copyright (C) 2018 ISUOG. Published by John Wiley & Sons Ltd.
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