COL1A1基因新的剪接突变c．3208G〉A导致I型成骨不全一家系

A novel splicing mutation in COL1A1 gene caused type I osteogenesis imperfecta in a Chinese family

目的探讨一个成骨不全家系中COL1A1基因的突变。方法收集一个成骨不全家系的临床资料，采用聚合酶链反应以及直接测序法对所有成员进行COL1A1基因突变的检测，同时在20名健康亲属以及200名非亲属对照中对发现的突变进行检测。结果RNA剪接分析发现一个C．3208G〉A突变，后者造成了一种新的剪接位点，从而导致移码突变。在患者的健康亲属及正常对照中未发现同样的突变。结论COL1A1基因突变是导致成骨不全的主要原因之一，本研究结果进一步丰富了I型胶原基因的突变谱。

Objective To study a family affected with osteogenesis imperfecta for potential mutations in COL1A1 gene. Methods Clinical data of an affected family was collected. Potential mutation of the COL1A1 gene was screened using polymerase chain reaction and direct sequencing. Suspected mutation was detected in 20 unaffected relatives and 200 unrelated healthy controls. Results Analysis of RNA splicing has revealed a c. 3208G/A mutation, which created a new splice sites and led to a frameshift mutation. The same mutation was not detected in the unaffected relatives or the 200 healthy controls. Conclusion Mutations of the COL1A1 gene are one of the major causes of osteogenesis imperfecta in Chinese population. Our finding has enriched the mutation spectrum of type I collagen genes.