背景:胎儿先天性心脏病(CHD)是最常见的先天性心脏病,发病率为0.6-0.8%,占婴儿先天性疾病死亡人数的30-50%。冠心病的发病机制尚不清楚,因此,积极有效的产前诊断对冠心病的预防和控制非常重要。在这里,据报道,中国CHD患者在DNAH9基因中具有罕见的复合杂合突变,预测了DNAH9蛋白的三维结构和功能变化。病例介绍:一名23岁的孕妇在妊娠27周时来我院进行产前诊断。她和她的伴侣都没有受到影响。通过超声筛查检测胎儿CHD。拷贝数变异测序(CNV-seq)揭示了在chr17p12(11,486,795-11,568,385)处的81kb缺失,包括DNAH9基因的外显子1-15,在心脏发育中起着关键作用。然后,使用全外显子组测序(WES),并在DNAH9中鉴定出无义突变(c.10975C>T),该突变导致从谷氨酰胺到终止的氨基酸3,659突变。使用SWISS-MODEL预测了3D突变蛋白结构,并显示了从功能性β-折叠和α-螺旋到终止的结构变化,分别。结论:我们描述了一例由DNAH9突变引起的胎儿CHD,并为识别基因内缺失提供了有效的诊断技术。该诊断过程可能涉及CHD的产前诊断。
Background: Fetal congenital heart disease (CHD) is the most common congenital defect, with an incidence of 0.6-0.8%, accounting for 30-50% of infant congenital disease deaths. The pathogenesis of CHD is still unclear, so an active and effective prenatal diagnosis is very important for the prevention and control of CHD. Herein, a Chinese CHD patient with rare compound heterozygous mutations in the DNAH9 gene was reported, and the 3D structure and functional changes of DNAH9 protein were predicted.
Case presentation: A 23-year-old pregnant woman came to our hospital for prenatal diagnosis at 27 weeks of gestation. Both she and her partner were unaffected. Fetal CHD was detected by ultrasound screening. Copy number variation sequencing (CNV-seq) revealed an 81 kb deletion at chr17p12 (11,486,795-11,568,385), including exons 1-15 of DNAH9 gene, which plays a key role in cardiac development. Then, whole exome sequencing (WES) was used and identified a nonsense mutation (c.10975C>T) in DNAH9, which resulted in the mutation of amino acid 3,659 from glutamine to termination. The 3D mutant protein structures were predicted using SWISS-MODEL and showed structural changes from functional β-sheet and α-helix to termination, respectively. Conclusion: We describe a
case of fetal CHD caused by DNAH9 mutations and provide an effective diagnostic technique for identifying intragenic deletions. This diagnostic process can be implicated in prenatal diagnosis of CHD.