房室间隔缺损（AVSD）为一组特殊类型的先天性心脏病，自然预后较差。其主要的致病机制为心内膜垫发育异常，但具体发病分子机制尚远未阐明。SOX7主要参与血管发育的调控，目前尚未见其在心内膜垫发育中的研究。我们前期在100例AVSD病人中筛到一个包含SOX7基因的片段缺失；研究发现其主要表达在人和小鼠的心内膜细胞；SOX7心内膜特异性敲除小鼠胚胎出现AVSD表型，且心内膜垫内皮-间充质转化（EndMT）过程明显受损；转录组分析结果显示BMP2在敲除小鼠心内膜垫中明显减少，外源添加BMP2部分回补SOX7敲除引起的EndMT受损，提示SOX7可能通过BMP信号通路影响房室间隔的形成。本项目将全面研究SOX7是如何调控BMP2，通过BMP2信号通路影响心内膜垫EndMT过程，最终参与房室间隔的形成。该项目不仅能发现AVSD新的致病基因，且将加深对先心病发病机制的理解，为先心病的诊治提供新策略。

Atrioventricular septal defect (AVSD) is a special type of congenital heart disease with poor natural prognosis. One of the main mechanisms of its occurrence and development is endocardial cushion dysplasia. However, the molecular mechanism of its occurrence is still far from clear. SOX7 is mainly involved in the regulation of vascular development, but its role in endocardial cushion development has not been studied yet. In our preliminary study, a deletion of SOX7 gene fragment and three missense mutations of SOX7 gene in 100 patients with atrioventricular septal defect were screened. Further studies showed that SOX7 protein was mainly expressed in human and mouse endocardial cells, atrioventricular septal defects were observed in SOX7 endocardial specific knockout mice during embryonic stage, and endothelial- mesenchymal transition (EndMT) was significantly impaired in the early stage of endocardial cushion. RNA-seq analysis showed that BMP2 was significantly reduced in the endocardial cushion of knockout mice, and exogenous addition of BMP2 recombinant protein rescued the damage of EndMT caused by SOX7 knockout, suggesting that SOX7 may affect the formation of atrioventricular septum through BMP signaling pathway. This project will comprehensively study how SOX7 regulates BMP2, influences endocardial cushion EndMT process through BMP2 and its downstream pathway, and ultimately participates in the regulation of atrioventricular septal formation. It is expected that the results of this study will not only discover new pathogenic genes for atrioventricular septal defect, but also deepen the understanding of the pathogenesis of congenital heart disease and provide new strategies for the diagnosis and prevention of congenital heart disease.