Wang Enshi, Nie Yu, Fan Xuesong, Zheng Zhe, Gu Haiyong, Zhang Hao, Hu Shengshou
Department of Cardiac Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, People's Republic of China.
J Genet. 2019 Jun;98(2).
Hypoplastic right heart syndrome(HRHS) is characterized by hypoplastic right ventricle (RV); Numerous transcriptional cascades in the second heart field (SHF) regulate RVdevelopment. The relationship of SHF gene variants with human HRHS remains unknown. The whole lengths of 17 SHF genes were sequenced in 16 HRHS, and the selected single-nucleotide variants (SNVs) were then genotyped in HRHS, other congenital heart disease (CHD) and healthy control. Luciferase assay was performed to verify the effect of : rs34221221A>GandTBX20: rs59854940C>Gat the transcription level. There were 151 (12.86%) novel SNVs after sequence analysis, of which three were in exons (one was synonymous SNV and two were nonsynonymous SNVs), two in promoter, and most SNVs (89.95%) were in intronic regions. Genotype analyses revealed that the minor alleles of : rs34221221 A>G and TBX20: rs59854940 C>G could increase HRHS risk (<0.05), but not in other CHD or healthy control. Luciferase assay showed that the minor G allele in rs34221221 significantly increased transcription while in rs59854940 it decreased TBX20 transcription significantly. Novel variants of SHF gene associated with HRHS were identified. Minor alleles in two variants from and could increase the risk of HRHS.
右心发育不全综合征（HRHS）的特征是右心室（RV）发育不全；第二心脏场（SHF）中的众多转录级联反应调节RV的发育。SHF基因变异与人类HRHS之间的关系尚不清楚。对16例HRHS患者的17个SHF基因全长进行测序，然后对HRHS、其他先天性心脏病（CHD）和健康对照者进行所选单核苷酸变异（SNV）的基因分型。进行荧光素酶测定以验证rs34221221A>G和TBX20：rs59854940C>G在转录水平上的作用。序列分析后有151个（12.86%）新的SNV，其中3个在外显子中（1个是同义SNV，2个是非同义SNV），2个在启动子中，大多数SNV（89.95%）在内含子区域。基因型分析显示，rs34221221 A>G和TBX20：rs59854940 C>G的次要等位基因可增加HRHS风险（<0.05），但在其他CHD或健康对照中则不然。荧光素酶测定表明，rs34221221中的次要G等位基因显著增加转录，而在rs59854940中则显著降低TBX20转录。鉴定出与HRHS相关的SHF基因新变异。来自[基因名称未给出]和TBX20的两个变异中的次要等位基因可增加HRHS风险。
