Abstract：
With the advancements in prenatal diagnostics, genome sequencing is now incorporated into clinical use to maximize the diagnostic yield following uninformative conventional tests (karyotype and chromosomal microarray analysis). Hong Kong started publicly funded prenatal genomic sequencing as a sequential test in the investigation of fetal structural anomalies in April 2021. The objective of the study was to evaluate the clinical performance and usefulness of this new service over one year. We established a web-based multidisciplinary team to facilitate case selection among the expert members. We retrospectively analyzed the fetal phenotypes, test results, turnaround time and clinical impact in the first 15 whole exome sequencing and 14 whole genome sequencing. Overall, the molecular diagnostic rate was 37.9% (11/29). De novo autosomal dominant disorders accounted for 72.7% (8/11), inherited autosomal recessive disorders for 18.2% (2/11), and inherited X-linked disorders for 9.1% (1/11). The median turnaround time for ongoing pregnancy was 19.5 days (range, 13-31 days). Our study showed an overall clinical impact of 55.2% (16/29), which influenced reproductive decision-making in four cases, guided perinatal management in two cases and helped future family planning in ten cases. In conclusion, our findings support the important role of genome sequencing services in the prenatal diagnosis of fetal structural anomalies in a population setting. It is important to adopt a multidisciplinary team approach to support the comprehensive genetic service.
摘要：
随着产前诊断的进步，基因组测序现已纳入临床应用,以在无信息的常规测试(核型和染色体微阵列分析)后最大化诊断产量.香港于2021年4月开始了公共资助的产前基因组测序，作为胎儿结构异常调查的顺序测试。该研究的目的是评估这项新服务在一年内的临床性能和实用性。我们建立了一个基于网络的多学科团队，以促进专家成员之间的案例选择。我们回顾性分析胎儿表型，测试结果,前15个全外显子组测序和14个全基因组测序的周转时间和临床影响。总的来说,分子诊断率为37.9%(11/29)。从头常染色体显性疾病占72.7%(8/11),遗传性常染色体隐性遗传疾病占18.2%(2/11)，遗传性X连锁疾病占9.1%(1/11)。持续怀孕的中位周转时间为19.5天(范围，13-31天）。我们的研究表明，总体临床影响为55.2%(16/29)，在四种情况下影响了生殖决策，指导围产期管理2例，帮助未来计划生育10例。总之,我们的研究结果支持基因组测序服务在人群胎儿结构异常产前诊断中的重要作用.重要的是采取多学科的团队方法来支持全面的遗传服务。
