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.
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。