Whole exome sequencing of fetal structural anomalies detected by ultrasonography
Whole exome sequencing of fetal structural anomalies detected by ultrasonography
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DOI：
10.1038/s10038-020-00869-8
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发表时间：
2020-11-03
影响因子：
3.5
通讯作者：
Matsumoto, Naomichi
中科院分区：
文献类型：
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作者：
Aoi, Hiromi;Mizuguchi, Takeshi;Matsumoto, Naomichi
本研究的目的是评估全外显子组测序（WES）在超声检查胎儿结构异常病例的遗传诊断中的作用。对19例产前结构异常患者进行WES检查。从出生后不久获得的脐带或脐带血中提取基因组DNA。WES数据仅对产前表型进行分析，并在获得有关产后表型的信息后重新分析数据。仅根据胎儿表型、致病性或可能致病性，19例中有5例（26.3%）发现单核苷酸变异。此外，我们通过基于wes的拷贝数变异分析检测了2例21三体。总诊断率为36.8%（7/19）。它们都符合各自的胎儿结构异常。通过参考出生后表型信息，另一个候选变异是通过产前筛查中未检测到的出生后临床特征确定的。由于在WES分析中，详细的表型是更好的诊断率所需要的，我们应该意识到胎儿表型是一个有用的，但有时有限的信息来源，以进行全面的遗传分析。收集更多基因型-表型相关性的数据，特别是在产前环境中适当评估WES的有效性是很重要的。
The objective of this study was to evaluate the efficacy of whole exome sequencing (WES) for the genetic diagnosis of cases presenting with fetal structural anomalies detected by ultrasonography. WES was performed on 19 cases with prenatal structural anomalies. Genomic DNA was extracted from umbilical cords or umbilical blood obtained shortly after birth. WES data were analyzed on prenatal phenotypes alone, and the data were re-analyzed after information regarding the postnatal phenotype was obtained. Based solely on the fetal phenotype, pathogenic, or likely pathogenic, single nucleotide variants were identified in 5 of 19 (26.3%) cases. Moreover, we detected trisomy 21 in two cases by WES-based copy number variation analysis. The overall diagnostic rate was 36.8% (7/19). They were all compatible with respective fetal structural anomalies. By referring to postnatal phenotype information, another candidate variant was identified by a postnatal clinical feature that was not detected in prenatal screening. As detailed phenotyping is desirable for better diagnostic rates in WES analysis, we should be aware that fetal phenotype is a useful, but sometimes limited source of information for comprehensive genetic analysis. It is important to amass more data of genotype-phenotype correlations, especially to appropriately assess the validity of WES in prenatal settings.