Copy Number Variations with Isolated Fetal Ventriculomegaly
Copy Number Variations with Isolated Fetal Ventriculomegaly
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孤立性胎儿脑室扩大的拷贝数变异
DOI：
10.2174/1566524017666170303125529
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发表时间：
2017-01-01
影响因子：
2.5
通讯作者：
Xu, Z.
中科院分区：
文献类型：
--
作者：
Hu, P.;Wang, Y.;Xu, Z.
背景：拷贝数变异（CNV）是许多神经发育障碍（ND）的重要遗传原因。然而，CNV 与胎儿孤立性轻度脑室扩大 (IMV) 的发生和预后之间的关联尚不清楚。 目的：探讨 CNV 与胎儿 IMV 发生之间可能存在的关联。 方法：这项回顾性研究招募了 154 名经超声确诊胎儿 IMV 的受试者，以及对照组中的 190 名接受高危产前血清筛查项目的受试者。排除标准包括胎儿G带染色体异常或胎儿TORCH感染阳性。通过 SNP 阵列检查了所有 344 个胎儿的 DNA 样本。在产后随访期间评估发育结果。结果：154 个 IMV 胎儿中的 13 个中发现了 14 个致病性 CNV (pCNV)。产前筛查高危人群190名受试者中有3名发现3个pCNV，差异显着（P值=0.016，X2检验）。值得注意的是，IMV 队列中检测到的 14 个 pCNV 均与神经发育障碍 (ND) 相关，包括自闭症、智力障碍。在 13 名携带 pCNV 的 IMV 胎儿中，有 5 名受试者在产后随访中发现出现 ND，其中两名患有自闭症，三名患有轻度神经发育迟缓。另外8名受试者包括3名12个月以下的正常婴儿，2名失访，3名终止妊娠。在 141 名未检测到 pCNV 的 IMV 受试者中，123 名受试者发育正常，16 名受试者失访，2 名受试者因胎儿脑积水或胎儿发育后期先天性心脏病而终止妊娠。结论：本研究表明 pCNV 与胎儿 IMV 之间存在关联。 pCNVs可能参与胎儿IMV和产后ND的病理过程。识别特定的基因组改变可以深入了解发病机制，并有助于更好地诊断和预测胎儿 IMV 的神经发育结果。
Background: Copy Number Variations (CNVs) are an important genetic cause of a number of neurodevelopmental disorders (NDs). However, the association between CNVs and the development and prognosis of fetal isolated mild ventriculomegaly (IMV) is unclear.Objectives: To investigate possible associations between CNVs and the development of fetal IMV.Methods: This retrospective study recruited 154 subjects with ultrasound-confirmed fetal IMV and 190 subjects in a control cohort who underwent a high-risk prenatal serum screening program. The exclusion criteria included fetus G-banding chromosomal abnormality or positive fetus TORCH infection. DNA samples from all 344 fetuses were examined by an SNP-array. Developmental outcomes were assessed during postnatal follow-up.Results: Fourteen pathogenic CNVs (pCNVs) were identified in 13 out of 154 IMV fetuses. Three pCNVs were found in 3 out of 190 subjects in the prenatal screening high-risk cohort, with a significant difference (P value= 0.016, X2 test). Notably, the 14 pCNVs detected in the IMV cohort were all associated with neurodevelopmental disorders (NDs), including autism, intellectual disability. Among the 13 IMV fetuses carrying pCNVs, five subjects were found in the postnatal follow-up to manifest NDs, including two with autism and three with mild neurodevelopmental delay. The other 8 subjects consisted of three normal infants younger than 12-months old, two lost in the follow-up, and three with the termination of pregnancy. Out of 141 IMV subjects without detectable pCNVs, 123 subjects showed normal development, 16 were lost in the follow-up, 2 subjects terminated the pregnancy due to fetal hydrocephalus or congenital heart disease in the late fetus development.Conclusions: This study suggests an association between pCNVs and fetal IMV. pCNVs may be involved in the pathological process of fetal IMV and postnatal NDs. Identifying specific genomic alterations may provide an insight into pathogenetic mechanism and aid better diagnosis and prognosis of neurodevelopmental outcomes in fetal IMV.