Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, 610041, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, 610041, China.
BMC Genomics. 2022 Feb 2;23(1):94. doi: 10.1186/s12864-022-08340-y.
The broad application of high-resolution chromosome detection technology in prenatal diagnosis has identified copy number loss (CNL) involving autosomal dominant (AD) genes in certain fetuses. Exon sequencing of fetuses exhibiting structural anomalies yields diagnostic information in up to 20% of cases. However, there is currently no relevant literature about the genetic origin and pregnancy outcome of CNL involving AD genes in fetuses without structural abnormalities.
This was a prospective study involving pregnant women who underwent amniocentesis for fetal copy number variation sequencing (CNVseq). Detection of parent-of-origin was suggested in cases of samples with CNL involving AD genes and the pregnancy outcome was monitored. Amniotic fluid samples from 24,844 fetuses without structural abnormalities were successfully tested via CNVseq. The results showed that 134 fetuses (0.5%) had small CNL (< 10 Mb) containing AD genes, after excluding microdeletion and microduplication syndrome and polymorphisms. By monitoring the pregnancy outcomes of the 134 fetuses, we found that 104 (77.6%) were good, 13 (9.7%) were adverse, and 17 (12.7%) pregnant women voluntarily chose to terminate pregnancy. Of the 13 fetuses with adverse pregnancy outcomes, only 2 fetuses had phenotypes consistent with those of diseases caused by AD genes involved in CNL.
The overall prognosis for fetuses without family history or structural abnormalities but with small CNL containing AD genes detected during pregnancy is good. The genetic origin, overlap status of established haploinsufficient gene and/or region, size of the CNL, and genetic mode may affect the pathogenicity of the CNL.
高通量染色体检测技术在产前诊断中的广泛应用，鉴定了某些胎儿中涉及常染色体显性（AD）基因的拷贝数丢失（CNL）。对表现出结构异常的胎儿进行外显子测序，在多达 20%的病例中可获得诊断信息。然而，目前尚无关于无结构异常胎儿中涉及 AD 基因的 CNL 的遗传起源和妊娠结局的相关文献。
这是一项前瞻性研究，涉及接受羊水胎儿拷贝数变异测序（CNVseq）的孕妇。在涉及 AD 基因的 CNL 样本中，建议检测亲本来源，并监测妊娠结局。对 24844 例无结构异常的胎儿羊水样本进行了 CNVseq 成功检测。结果显示，在排除微缺失和微重复综合征和多态性后，有 134 例胎儿（0.5%）存在含有 AD 基因的小 CNL（<10 Mb）。通过监测 134 例胎儿的妊娠结局，我们发现 104 例（77.6%）良好，13 例（9.7%）不良，17 例（12.7%）孕妇自愿选择终止妊娠。在 13 例不良妊娠结局的胎儿中，只有 2 例具有与 AD 基因相关的 CNL 引起的疾病的表型一致。
对于无家族史或结构异常但在妊娠期间检测到含有 AD 基因的小 CNL 的胎儿，总体预后良好。遗传起源、已建立的单等位基因不足基因和/或区域的重叠状态、CNL 的大小和遗传方式可能影响 CNL 的致病性。
