先天性心脏病（先心病）是最常见的先天性畸形之一，严重危害着儿童的健康，其发生机制尚远未阐明。孟德尔遗传模式的先心病家系是寻找先心病新致病基因和阐释先心病发病机制的珍贵材料。在前期工作中，本课题组收集到一个极具研究价值的染色体显性遗传模式的先心病家系，前期通过先证者的全外显子测序分析与拷贝数变异分析排除已知先心病相关致病基因突变和拷贝数变异致病可能，提示该家系很可能由未知的先心病新致病基因导致。通过对家系患者的全外显子测序数据分析筛选、候选基因的初步功能分析推测FILIP1L可能为该家系致病基因，拟进一步通过候选基因表达模式检测、散发先心病患者突变分析、突变体蛋白功能分析、基因敲除小鼠模型等研究明确致病基因并探索其在胚胎心脏发育与畸形发生中的分子机制。本项目先心病新致病基因的克隆与功能研究将拓宽对心脏发育和分子致病机制的认识，为今后开发先心病的早期诊断、遗传咨询和治疗提供新方向。

Congenital heart disease (CHD), one of the most common congenital malformations, seriously endangers the health of children. The molecular mechanisms underlying heart development and CHD pathogenesis are still unclear. Mendelian genetics CHD pedigrees have been a valuable source of information in the research of novel causative genes identification and cardiac malformation pathogenesis. Previously we recruited an dominant inheritant CHD pedigree. Using exome sequencing and copy number variation assay on proband, we excluded causative mutations in known CHD genes and pathogenic copy number variations. These results suggested that the CHD in the pedigree is very likely caused by mutation in novel CHD genes. Then exome sequencing was performed on other CHD patients in the pedigree and primary function of candidate genes were analyzed. Results implied that FILIP1L may be the pathogenic gene in this CHD family. In the following studies, we will identify the causative gene and explore its molecular mechanism by expression pattern characterization, mutation analysis in sporadic CHD patients, functional analysis of mutant proteins, and study of gene knockout mouse model. This study may provide evidences for early diagnosis, genetic counseling and treatment for the congenital heart disease.