V型成骨不全患者的基因突变及临床特征

Genetic mutation and clinical features of osteogenesis imperfecta type V

目的探讨V型成骨不全（osteogenesis imperfecta，OI）患者的基因突变及临床特征。方法收集5例V型0I患者的临床资料，其中1例为家系患者。采集患者、随诊家属及正常对照者的静脉血，PCR扩增干扰素诱导跨膜蛋白5（interferon-induced transmembrane protein5，IFITM5）基因，基因测序确定突变位点。结果基因测序结果显示，5例患者均存在IFITM5基因的5＇非翻译区的一个碱基C转换成T（c．-14c〉T），1例家系患者的母亲为V型0I患者，也存在IFITM5基因的c．-14C〉T突变。所有患者均出现频繁骨折，并伴有脊柱和（或）四肢畸形，均无牙质发育不全、无听力障碍，1例患者有蓝色巩膜。X线片显示，5例患者均具有前臂骨间膜钙化；3例骨折处形成增生性骨痂；4例桡骨头脱位。结论5例V型OI患者均具有IFITM5基因杂合子突变（c．-14C〉T），患者具有独特的影像学特征，骨问膜钙化、增生性骨痂、桡骨头脱位等。

Objective To explore genetic mutations and clinical features of osteogenesis imperfecta type V. Methods Clinical record of five patients （including one familial case） with osteogenesis imperfeeta type V were retrospectively analyzed. Peripheral blood samples of the patients, one family member, as well as healthy controls were collected. Mutation of IFITM5 gene was identified by PCR amplification and Sanger sequencing. Results A heterozygous mutation （c. -14C〉T） in the 5＇ UTR of the IFITM5 gene was identified in all of the patients and one mother. The clinical findings included frequent fractures and spine and/or extremities deformities, absence of dentinogenesis imperfecta, absence of hearing impairment, and blue sclera in 1 case. Radiographic findings revealed calcification of the interosseous membrane between the radius-ulna in all cases. Hyperplastic callus formation was found in 3 cases. Four had radial-head dislocation. Conclusion A single heterozygous mutation e. -14C〉T was found in the 5＇ UTR of the IFITM5 gene in 5 patients with osteogensis imperfecta type V. The patients showed specific radiological features including calcification of interosseous membrane, hyperplastic callus formation, and radial-head dislocation.