全外显子组测序探寻脊柱肋骨发育不全致病基因的研究

Spondylocostal Dysostosis (SCD) is a severe malformation of spine, most of the patients lose their ability of motion due to spinal malformation or abnormal cardiorespiratory function，therefore, it will not only cause psychophysical problems but also bring high burden to families and society. Because of laking of early prediction methods, most patients were found in their late phase. Therefore, it is important to detect new diagnostic method and therapeutic target. Reported genes related with SCD could only cover very few cases. Some somitic developing related genes mutation in the level of exome may cause the occurrence of SCD, and the clinical type and progression of SCD may also be determined by these mutations. Our group previously reported some SNPs and exomes in orthopedics diseases.In this project, whole exome sequencing will be used with the strategy of PPC family pedigrees combining with sporadic cases，further identification will also be done in another cases and normal population sample.In vitro experiment will be used in this project to analysis suspected genes. Our aim is to find genes related to the onset and development of SCD, to provide theoretical foundation of genetic and biomolecular etiology, to explore new clinical/genetics typing, furthermore, to provide practical basis of early diagnosis and treatment of SCD.

脊柱肋骨发育不全（Spondylocostal Dysostosis,SCD）是一种严重致残性先天性疾病，可导致身体和心理问题，给家庭和社会造成极大负担。因缺乏早期预测手段，多在出现严重脊柱畸形才被发现，治疗方法只能以支具或手术控制病情发展，因此，探索早期诊断方法和病因治疗靶点是当前SCD的研究热点。目前已报道突变基因仅能解释个别病例，某些体节发育相关基因的外显子水平突变可能导致SCD的发生，并决定SCD不同的表型及进展。在前期骨科遗传学研究基础上，本项目拟采用全外显子组测序方法，通过核心家系结合散发病例的研究策略，并在大样本人群、体外细胞实验两个层面进行验证，确定与SCD发生发展相关的基因，为预测疾病发展和指导临床早期干预时机提供理论依据，探寻SCD的个体化早期诊断和治疗措施。

脊柱肋骨发育不全（Spondylocostal Dysostosis, SCD）是一种严重致残性先天性疾病，可导致身体和心理问题，给家庭和社会造成极大负担。因缺乏早期预测手段，多在出现严重脊柱畸形才被发现，治疗方法只能以支具或手术控制病情发展，因此，探索早期诊断方法和病因治疗靶点是当前SCD的研究热点。目前已报道突变基因仅能解释个别病例，某些体节发育相关基因的外显子水平突变可能导致SCD的发生，并决定SCD不同的表型及进展。在前期骨科遗传学研究基础上，本项目采用了全外显子组测序方法，通过核心家系结合散发病例的研究策略，并在大样本人群、体外细胞功能实验两个层面进行验证，确定与SCD发生发展相关的基因如MYH3,FLNB等基因以及其潜在的功能改变，为预测疾病发展和指导临床早期干预时机提供理论依据，探寻SCD的个体化早期诊断和治疗措施。