PDF(Pubmed)
Abstract：
To evaluate the genetic etiology of fetal dextrocardia, associated ultrasound anomalies, and perinatal outcomes, we investigated the utility of whole exome sequencing (WES) for prenatal diagnosis of dextrocardia. Fetuses with dextrocardia were prospectively collected between January 2016 and December 2022. Trio-WES was performed on fetuses with dextrocardia, following normal karyotyping and/or chromosomal microarray analysis (CMA) results. A total of 29 fetuses with dextrocardia were collected, including 27 (93.1%) diagnosed with situs inversus totalis and 2 (6.9%) with situs inversus partialis. Cardiac malformations were present in nine cases, extra-cardiac anomalies were found in seven cases, and both cardiac and extra-cardiac malformations were identified in one case. The fetal karyotypes and CMA results of 29 cases were normal. Of the 29 cases with dextrocardia, 15 underwent WES, and the other 14 cases refused. Of the 15 cases that underwent WES, clinically relevant variants were identified in 5/15 (33.3%) cases, including the diagnostic variants DNAH5, DNAH11, LRRC56, PEX10, and ZIC3, which were verified by Sanger sequencing. Of the 10 cases with non-diagnostic results via WES, eight (80%) chose to continue the pregnancies. Of the 29 fetuses with dextrocardia, 10 were terminated during pregnancy, and 19 were live born. Fetal dextrocardia is often accompanied by cardiac and extra-cardiac anomalies, and fetal dextrocardia accompanied by situs inversus is associated with a high risk of primary ciliary dyskinesia. Trio-WES is recommended following normal karyotyping and CMA results because it can improve the diagnostic utility of genetic variants of fetal dextrocardia, accurately predict fetal prognosis, and guide perinatal management and the reproductive decisions of affected families.
摘要：
探讨胎儿右位心的遗传学病因,相关的超声异常，和围产期结局，我们研究了全外显子组测序(WES)在右位心产前诊断中的应用。在2016年1月至2022年12月期间前瞻性收集患有右位心的胎儿。Trio-WES对有右位心的胎儿进行，正常核型分析和/或染色体微阵列分析（CMA）结果。共收集29例右位心胎儿，包括27例（93.1％）被诊断为完全倒位，2例（6.9％）被诊断为完全倒位。9例患者出现心脏畸形,在7例中发现了心脏外异常，在一例病例中发现了心脏和心脏外畸形。29例胎儿核型和CMA结果正常。29例右位心,15人接受了WES，其他14个案件被拒绝。在15例接受WES的病例中，在5/15（33.3％）病例中发现了临床相关变异，包括诊断变异体DNAH5,DNAH11,LRRC56,PEX10和ZIC3,通过Sanger测序验证.在通过WES没有诊断结果的10例病例中，八人(80%)选择继续怀孕。在29个患有右位心的胎儿中，10人在怀孕期间被终止，19人是活生生的。胎儿右位心通常伴有心脏和心脏外异常，胎儿右位心伴发位置反肌与原发性纤毛运动障碍的高风险相关。在正常的核型分析和CMA结果后，建议使用Trio-WES，因为它可以提高胎儿右位心遗传变异的诊断实用性。准确预测胎儿预后，并指导围产期管理和受影响家庭的生殖决策。
