随着高通量测序技术的发展，遗传性疾病的分子诊断即将进入新纪元。遗传代谢性骨病是一类影响骨骼生长发育和骨代谢异常的遗传性疾病，由于其临床表现的同质性及致病基因的异质性，准确的分子诊断对于临床诊治和阐明疾病的发病机制，提高对骨骼发育和骨代谢的调控意义重大。新近发展的目标基因捕获结合及第二代高通量测序平台是一种相比传统Sanger测序及全外显子测序更敏感、更快速、更经济的新方法，在各领域均已展现出良好的应用前景。本研究旨在利用此项技术建立快速高通量的遗传性骨病致病基因检测技术系统，其中涵盖主要遗传(代谢)性骨病的相关致病基因，以及骨骼生长发育和骨代谢调控通路关键蛋白的编码基因400多个。并利用本课题组以及积累丰富的临床资料和遗传学样本库，对该系统进行充分的验证。探索该方法作为新的临床分子诊断方法在遗传（代谢）性骨病中应用的可能性，建立起国际第一个大型遗传（代谢）性骨病快速高通量分子诊断平台。

Genetic （metabolic）skeletal diseases are a heterogeneous group of more than 350 inherited disorders frequently associated with orthopedic complications and varying degrees of dwarfism or short stature. The fact that the pathogenic genes are located at all parts of the skeletal metabolic regulatory pathway makes them ideal models for the research on the regulatory network of skeletal metabolism.And the accurate molecular diagnosis is of great important to both the clinical treatment as well as the following researches. The emerging targeted gene capture combined with next-generation sequencing provides a more sensitive, rapid, economic and promising method for the molecular diagnosis of the diseases.In the research we aim to establish and validate a high throughput sequencing panel including 400 genes related to skeletal diseases, and to explore its utility in clinical diagnostics of genetic (metabolic) skeletal diseases.