Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management
Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management
复制标题
DOI：
10.1038/gim.2018.30
复制
发表时间：
2018-11-01
影响因子：
8.8
通讯作者：
Chitty, Lyn S.
中科院分区：
文献类型：
--
作者：
Chandler, Natalie;Best, Sunayna;Chitty, Lyn S.
目的：2-5%的妊娠发生意外的胎儿异常。虽然传统的细胞遗传学和微阵列方法在大约40%的病例中实现了诊断，但其他病例缺乏诊断阻碍了父母咨询，知情决策和妊娠管理。出生后外显子组测序产生高诊断率，但依赖于仔细的表型分析来解释基因型结果。在这里，我们使用了一个多学科的方法来探讨胎儿外显子组快速测序产前诊断使用骨骼发育不良作为exemplar.Methods的效用：父母在怀孕进行侵入性检测，因为超声胎儿异常，多学科的审查认为骨骼发育不良可能的病因，同意外显子组三重测序（父母和胎儿）。变异的解释集中在一个虚拟面板的240个基因已知会导致骨骼dysplasia.Results：在13/16（81%）的情况下作出了连续性分子诊断。在某些情况下，胎儿超声检查结果本身就足以让父母选择终止妊娠。在其他人中，分子诊断告知准确的预测结果，改善父母的咨询，并使父母终止或继续妊娠certainly.Conclusion：三重测序与专家多学科的审查，病例选择和数据解释产量及时，高诊断率的胎儿出现意外的骨骼异常。这改善了父母咨询和怀孕管理。
Purpose: Unexpected fetal abnormalities occur in 2-5% of pregnancies. While traditional cytogenetic and microarray approaches achieve diagnosis in around 40% of cases, lack of diagnosis in others impedes parental counseling, informed decision making, and pregnancy management. Postnatally exome sequencing yields high diagnostic rates, but relies on careful phenotyping to interpret genotype results. Here we used a multidisciplinary approach to explore the utility of rapid fetal exome sequencing for prenatal diagnosis using skeletal dysplasias as an exemplar.Methods: Parents in pregnancies undergoing invasive testing because of sonographic fetal abnormalities, where multidisciplinary review considered skeletal dysplasia a likely etiology, were consented for exome trio sequencing (both parents and fetus). Variant interpretation focused on a virtual panel of 240 genes known to cause skeletal dysplasias.Results: Definitive molecular diagnosis was made in 13/16 (81%) cases. In some cases, fetal ultrasound findings alone were of sufficient severity for parents to opt for termination. In others, molecular diagnosis informed accurate prediction of outcome, improved parental counseling, and enabled parents to terminate or continue the pregnancy with certainty.Conclusion: Trio sequencing with expert multidisciplinary review for case selection and data interpretation yields timely, high diagnostic rates in fetuses presenting with unexpected skeletal abnormalities. This improves parental counseling and pregnancy management.