我们业已阐明了部分青壮年不明原因夜间睡眠中猝死综合征（SUNDS）的分子病因，但至今仍有约80%的SUNDS难于捕获到原发病因。新近的重大科学发现揭示心肌电稳定性与睡眠、代谢、呼吸等生物节律一样受生物钟基因的复杂调控。我们认为，具有显著生物节律特征（猝死于夜间睡眠，突发心电失稳）的SUNDS中应蕴含丰富的生物钟基因致病突变信息。为突破SUNDS病因研究瓶颈，与国际同行抢占疾病信息发掘的先机，拟在前期建立的心脏离子通道基因病变谱的基础上，发掘SUNDS生物钟基因的遗传变异资源，筛选出可疑分子病因；在人源性诱导多能干细胞分化心肌中研究突变体的细胞电生理功能，确立致病突变体；在转基因小鼠动物整体水平探索功能表型显著异常的突变体的致病机制。籍此，以期发现SUNDS新的易感基因，丰富SUNDS的分子病变谱，为进一步解析SUNDS的发生机制、完善其分子病理学诊断、探寻其综合防治方法提供科学依据。

The genetic cause of sudden unexplained nocturnal death syndrome （SUNDS）in part cases was elucidated in previous studies by our group. Currently, the etiology of about 80% of SUNDS cases remains unknown. But recently, a breakthrough in the research of circadian clocks showed that circadian rhythm genes govern cardiac repolarization and arrhythmogenesis (cardiac electrophysiological stabilities), just like circadian rhythm genes control sleep, metabolism, and respiration. We hypothesize that there are numerous pathogenic variants of circadian rhythm genes in SUNDS due to its prominent circadian characters (sudden cardiac electical instability during nocturnal sleep). To break through the bottleneck of etiological research on SUNDS and to explore opportunities with international researchers in seeking pathogenic variants in SUNDS, we plan to perform the following research: Based on the previous database (diseases spectrum) of cardiac ion channel gene variants that we established, variants in the circadian clock genes of SUNDS victims will be screened to find the plausible molecular etiology of SUNDS. Cellular electrophysiological studies will be performed of these variants in human induced pluripotent stem cell derived cardiomyocytes to identify if they are pathogenic mutations. Mutations with obvious functional phenotypes will be chosen to make transgenic mice that address the mechanisms by which SUNDS occur in an animal model of disease. Through these studies, we expect to find new susceptible SUNDS genes, enlarge the database of molecular pathology of SUNDS, and provide scientific evidences for elucidating the mechanisms of SUNDS, improving its molecular pathological diagnosis, and exploring prevention methods.