外显子组测序在结构正常胎儿中的应用——结果与伦理问题。
Exome sequencing for structurally normal fetuses-yields and ethical issues.
机构信息
Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel.
Department of Genetics, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
出版信息
Eur J Hum Genet. 2023 Feb;31(2):164-168. doi: 10.1038/s41431-022-01169-9. Epub 2022 Sep 7.
The yield of chromosomal microarray analysis (CMA) is well established in structurally normal fetuses (0.4-1.4%). We aimed to determine the incremental yield of exome sequencing (ES) in this population. From February 2017 to April 2022, 1,526 fetuses were subjected to ES; 482 of them were structurally normal (31.6%). Only pathogenic and likely pathogenic (P/LP) variants, per the American College of Medical Genetics and Genomics (ACMG) classification, were reported. Additionally, ACMG secondary findings relevant to childhood were reported. Four fetuses (4/482; 0.8%) had P/LP variants indicating a moderate to severe disease in ATP7B, NR2E3, SPRED1 and FGFR3, causing Wilson disease, Enhanced S-cone syndrome, Legius and Muenke syndromes, respectively. Two fetuses had secondary findings, in RET and DSP. Our data suggest that offering only CMA for structurally normal fetuses may provide false reassurance. Prenatal ES mandates restrictive analysis and careful management combined with pre and post-test genetic counseling.
染色体微阵列分析 (CMA) 的检出率在结构正常的胎儿中已得到充分证实（0.4-1.4%）。我们旨在确定外显子组测序 (ES) 在该人群中的增量检出率。从 2017 年 2 月到 2022 年 4 月，对 1526 例胎儿进行了 ES 检测；其中 482 例结构正常（31.6%）。仅报告符合美国医学遗传学与基因组学学会 (ACMG) 分类的致病性和可能致病性 (P/LP) 变异。此外，还报告了与儿童期相关的 ACMG 次要发现。有 4 例胎儿（4/482；0.8%）存在 P/LP 变异，提示 ATP7B、NR2E3、SPRED1 和 FGFR3 中存在中度至重度疾病，分别导致威尔逊病、增强 S-锥体综合征、Legius 和 Muenke 综合征。有 2 例胎儿存在次要发现，分别在 RET 和 DSP 中。我们的数据表明，仅为结构正常的胎儿提供 CMA 可能会提供错误的保证。产前 ES 需要进行限制性分析和谨慎管理，并结合产前和产后遗传咨询。
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