青少年特发性脊柱侧凸(adolescent idiopathic scoliosis, AIS) 是青少年最常见的脊柱畸形，发病率约为1-3%，好发于10-16岁的青少年，以女性多见，其发病机制复杂。课题组前期研究中收集了一个AIS大家系和23例散发样本，采用外显子组序列捕获结合第二代测序技术，在IS6基因编码产物上发现了AIS致病突变并将其成功克隆，该突变导致IS6基因编码产物发生E882A（谷氨酸→丙氨酸）的改变。并证实IS6基因编码产物上存在PKA及其它信号分子结合的区域。本项目拟对致病基因IS6开展进一步研究，探讨该突变对cAMP/PKA通路及其它相关信号通路介导的调控蛋白与靶基因调控序列结合的影响及其参与AIS发生、发展的病理过程，从而揭示IS6基因突变导致脊柱侧凸的分子机制，为临床诊断、预防、治疗及新药的研制开发提供理论依据。

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affects 1~3% of children in the at-risk population of those aged 10~16 years, and predominantly affects girls. The pathogenesis of AIS is complicated. In our previous study, we have found the mutation of IS6 in a rare AIS pedigree and 23 cases of sporadic samples using exome sequence capture combined with second-generation sequencing and bioinformatics analysis, and cloned it successfully. Because of the mutation of IS6, which coding product occurs E882A change (glutamic acid→alanine). Moreover, we found there were many binding domain for PKA and other signaling molecules by detecting IS6 coding product. Therefore, this study will be carried out for further study of IS6 to clarify the mutation impact on cAMP/PKA and other pathway involved in the pathological process of AIS. We hope to clarify the pathogenesis of AIS from the mutation of IS6, which will be a great help in disease prevention, early diagnosis and treatment of AIS.

青少年特发性脊柱侧凸(adolescent idiopathic scoliosis, AIS) 是青少年最常见的 脊柱畸形，发病率约为 1-3%，好发于 10-16 岁的青少年，以女性多见，其发病机制复杂。课 题组前期研究中收集了一个 AIS 大家系和 23 例散发样本，采用外显子组序列捕获结合第二 代测序技术，在AKAP2 基因编码产物上发现了 AIS 致病突变并将其成功克隆，该突变导致 AKAP2 基因编码产物发生 E882A（谷氨酸→丙氨酸）的改变。并证实AKAP2基因编码产物上存在 PKA 及其它信号分子结合的区域。本项目对致病基因 AKAP2 开展进一步研究，研究结果确认了AKAP2基因野生型及突变体在细胞内的表达、定位及降解，确认了AKAP2 与 PRKAR2A 的相互作用，但在其通路中的活性作用未能得到明确的结果。