家族性肥厚型心肌病（FHC）是主要由肌节功能异常引起的常染色体显性遗传性心血管疾病。调节肌球蛋白轻链（RLC）基因相关的FHC常导致严重的临床表型和心源性猝死等不良预后。该基因同一功能区的邻近突变可引发不同的表型，而不同功能区的突变却可能出现相似表型，其突变型-表型的发生机制显然不能简单地用功能区的相应损害来解释，也缺乏有效的干预手段。最近的研究显示，NRSF可调控心脏胚胎基因的再编程，而后者是引发FHC心肌重构和心电生理不稳定的主要原因之一。本研究在生物信息学分析和以往研究的基础上，建立FHC相关的人RLC的不同突变转基因斑马鱼模型，模拟人类FHC的表型，研究NRSF/ NRSE系统调控的心脏胚胎基因再编程与RLC的突变型-表型的关系，并尝试以此为干预靶点，从分子水平改善疾病的表型和预后，为个体化治疗做准备。

Familial hypertrophic cardiomyopathy (FHC) is mainly caused by autosomal dominant sarcomere genes mutations which relate to sarcomere function . Regulatory myosin light chain (RLC) related FHC often leads to severe clinical phenotypes and cardiac surden death. The gene mutations in the same functional area can cause different phenotypes, but the mutations in different functional areas may appear similar phenotypes. The mechanism about the genotype-phenotype can not be explained by the mutations related functional areas, and is lack of effective interventions. Recent studies have shown that NRSF can mediated cardiac fetal gene re-program which is involved in FHC myocardial remodeling and cardiac electrophysiological instability. On the basis of bioinformatics analysis and previous studies, we will establish FHC related RLC mutations transgenic zebrafish models and explore the relationship between the FHC related genotype-phenotype and NRSF / NRSE system mediated cardiac fetal genes re-program. This study may provide a potential target which may improve prognosis of FHC.