Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases
Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases
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DOI：
10.1002/mgg3.944
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发表时间：
2019-09-01
影响因子：
2
通讯作者：
Kong, Xiangdong
中科院分区：
文献类型：
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作者：
Shi, Panlai;Li, Rui;Kong, Xiangdong
背景产前胎儿拷贝数变异的来源和变异类型，以及父母来源在解释胎儿拷贝数变异中的关键作用尚不清楚。方法选择141个CNV异常的产前核心家系，进行低覆盖率大规模平行CNV测序。结果72.3%的胎儿CNV来自父母，27.7%为新变异。杂合性缺失63例，三重重复70例，复杂缺失和重复6例，四重重复2例。这意味着杂合缺失和复制的比率大约为1。此外，在父母来源的胎儿异常CNV报告中，在确认父母来源之前，62个CNV是意义不明的变异(VUS)，15个CNV可能是良性的，20个CNV可能是致病的，5个CNV是致病的。然而，在确认亲本来源后，总的临床意义变为12个VUS，可能是良性的，1个可能是致病的，0个致病。检测到亲代CNV后，78.4%的胎儿CNV的临床意义发生改变，趋于良性。此外，我们还追踪了所有的家庭。新突变组93.3%的双亲衍生胎儿和30.3%的胎儿出生健康。结论父母来源确认对解释胎儿CNV的临床意义具有重要意义。
Background The sources and variants types of the copy number variations (CNVs) in prenatal fetal, and the critical role of parental origin on the interpretation of fetal CNVs are unclear. Methods One hundred and forty-one prenatal core families with abnormal CNVs were selected and performed by low-coverage massively parallel CNV sequencing (CNV-seq). Results The data showed that 72.3% of fetal CNVs were derived from parents, and 27.7% were new variations. Sixty-three cases were heterozygous deletion, 70 cases were threefold duplication, six cases were complex deletion and duplication, and two cases were fourfold repeats. That means the rate of heterozygous deletion and duplication was approximate one. In addition, in parental-derived fetal abnormal CNVs reports, before validating parental origin, 62 CNVs were variants of uncertain significance (VUS), 15 CNVs were likely benign, 20 CNVs were likely pathogenic, and 5 CNVs were pathogenic. However, after validating parental origin, the total clinical significance changed into 12 VUS, 89 likely benign, 1 likely pathogenic, and 0 pathogenic. The clinical interpretation of 78.4% fetal CNVs was changed and tended to be benign after parental CNVs were detected. Besides, we followed up all families. 93.3% parental-derived fetal and 30.3% fetus in new mutation group were born healthy. Conclusion Parental origin verification has an important significance for interpretation on the clinical significance of fetal CNVs.