在 141 个核心家庭案例中，验证亲源性对胎儿拷贝数变异的临床解读的影响。
Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases.
机构信息
Genetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Genetic and Prenatal Screening Center, Maternal and Child Health Hospital of Jiaozuo, Jiozuo, China.
出版信息
Mol Genet Genomic Med. 2019 Oct;7(10):e00944. doi: 10.1002/mgg3.944. Epub 2019 Sep 1.
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.
背景
产前胎儿的拷贝数变异（CNV）的来源和变体类型，以及亲本来源对胎儿 CNV 解读的关键作用尚不清楚。
方法
选择 141 个具有异常 CNV 的产前核心家系，并通过低覆盖度大规模平行 CNV 测序（CNV-seq）进行检测。
结果
数据显示，72.3%的胎儿 CNV 来自父母，27.7%为新发变异。63 例为杂合性缺失，70 例为三倍体重复，6 例为复杂缺失和重复，2 例为四倍体重复。这意味着杂合性缺失和重复的发生率大致相同。此外，在报道来自父母的胎儿异常 CNV 中，在验证亲本来源之前，62 个 CNV 为意义不明的变异（VUS），15 个 CNV 为可能良性，20 个 CNV 为可能致病性，5 个 CNV 为致病性。然而，在验证亲本来源后，总临床意义变为 12 个 VUS、89 个可能良性、1 个可能致病性和 0 个致病性。78.4%胎儿 CNV 的临床解读在检测到亲本 CNV 后发生了改变，趋于良性。此外，我们对所有家庭进行了随访。93.3%的亲本来源胎儿和 30.3%的新发突变组胎儿出生健康。
结论
亲本来源验证对胎儿 CNV 临床意义的解读具有重要意义。
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