Abstract：
Deleterious genetic variants comprise one cause of cardiac conotruncal defects (CTDs). Genes associated with CTDs are gradually being identified. In the present study, we aimed to explore the profile of genetic variants of CTD-associated genes in Chinese patients with non-syndromic CTDs.
Thirty-nine CTD-related genes were selected after reviewing published articles in NCBI, HGMD, OMIM, and HPO. In total, 605 patients with non-syndromic CTDs and 300 healthy controls, all of Han ethnicity, were recruited. High-throughput targeted sequencing was used to detect genetic variants in the protein-coding regions of genes. We performed rigorous variant-level filtrations to identify potentially damaging variants (Dvars) using prediction programs including CADD, SIFT, PolyPhen-2, and MutationTaster.
Dvars were detected in 66.7% (26/39) of the targeted CTD-associated genes. In total, 11.07% (67/605) of patients with non-syndromic CTDs were found to carry one or more Dvars in targeted CTD-associated genes. Dvars in FOXH1, TBX2, NFATC1, FOXC2, and FOXC1 were common in the CTD cohort (1.5% [9/605], 1.2% [7/605], 1.2% [7/605], 1% [6/605], and 0.5% [3/605], respectively).
Targeted exon sequencing is a cost-effective approach for the genetic diagnosis of CTDs. Our findings contribute to an understanding of the genetic architecture of non-syndromic CTDs.
Thirty-nine CTD-related genes were selected after reviewing published articles in NCBI, HGMD, OMIM, and HPO. In total, 605 patients with non-syndromic CTDs and 300 healthy controls, all of Han ethnicity, were recruited. High-throughput targeted sequencing was used to detect genetic variants in the protein-coding regions of genes. We performed rigorous variant-level filtrations to identify potentially damaging variants (Dvars) using prediction programs including CADD, SIFT, PolyPhen-2, and MutationTaster.
Dvars were detected in 66.7% (26/39) of the targeted CTD-associated genes. In total, 11.07% (67/605) of patients with non-syndromic CTDs were found to carry one or more Dvars in targeted CTD-associated genes. Dvars in FOXH1, TBX2, NFATC1, FOXC2, and FOXC1 were common in the CTD cohort (1.5% [9/605], 1.2% [7/605], 1.2% [7/605], 1% [6/605], and 0.5% [3/605], respectively).
Targeted exon sequencing is a cost-effective approach for the genetic diagnosis of CTDs. Our findings contribute to an understanding of the genetic architecture of non-syndromic CTDs.
摘要：
目的：有害的遗传变异是导致心脏截尾缺损（CTDs）的一个原因。与CTD相关的基因正在逐渐被识别。在本研究中,我们旨在探讨中国非综合征型CTDs患者CTD相关基因的遗传变异谱.
方法：在NCBI发表的文章后，选择了39个CTD相关基因，HGMD,OMIM,HPO。总的来说,605例非综合征型CTD患者和300例健康对照，所有汉族，被招募。高通量靶向测序用于检测基因蛋白质编码区的遗传变异。我们使用包括CADD在内的预测程序进行了严格的变体水平筛选，以识别潜在的破坏性变体（Dvars）。SIFT,PolyPhen-2和MutationTaster。
结果：在66.7％（26/39）的靶向CTD相关基因中检测到Dvars。总的来说,11.07%(67/605)的非综合征型CTD患者被发现在靶向CTD相关基因中携带一个或多个Dvars。FOXH1，TBX2，NFATC1，FOXC2和FOXC1中的Dvars在CTD队列中很常见（1.5％[9/605]，1.2%[7/605]，1.2%[7/605]，1%[6/605]，和0.5%[3/605]，分别)。
结论：靶向外显子测序是CTDs基因诊断的一种经济有效的方法。我们的发现有助于理解非综合征型CTD的遗传结构。
方法：在NCBI发表的文章后，选择了39个CTD相关基因，HGMD,OMIM,HPO。总的来说,605例非综合征型CTD患者和300例健康对照，所有汉族，被招募。高通量靶向测序用于检测基因蛋白质编码区的遗传变异。我们使用包括CADD在内的预测程序进行了严格的变体水平筛选，以识别潜在的破坏性变体（Dvars）。SIFT,PolyPhen-2和MutationTaster。
结果：在66.7％（26/39）的靶向CTD相关基因中检测到Dvars。总的来说,11.07%(67/605)的非综合征型CTD患者被发现在靶向CTD相关基因中携带一个或多个Dvars。FOXH1，TBX2，NFATC1，FOXC2和FOXC1中的Dvars在CTD队列中很常见（1.5％[9/605]，1.2%[7/605]，1.2%[7/605]，1%[6/605]，和0.5%[3/605]，分别)。
结论：靶向外显子测序是CTDs基因诊断的一种经济有效的方法。我们的发现有助于理解非综合征型CTD的遗传结构。
