Clinical and genetic analysis in 185 Chinese probands of osteogenesis imperfecta
Clinical and genetic analysis in 185 Chinese probands of osteogenesis imperfecta
复制标题
185例中国成骨不全症先证者临床及遗传学分析
DOI：
10.1007/s00774-020-01163-5
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发表时间：
2020-10-17
影响因子：
3.3
通讯作者：
Zhang, Zhen-Lin
中科院分区：
文献类型：
--
作者：
Xi, Lei;Zhang, Hao;Zhang, Zhen-Lin
引言
成骨不全症（OI）是一种众所周知的遗传性结缔组织疾病，其特征为骨骼脆弱和骨量低。近90%的成骨不全症患者在COL1A1和COL1A2基因中存在变异，这些基因编码I型胶原蛋白的α1链和α2链。
材料与方法
对2005年3月至2019年12月在上海交通大学附属第六人民医院确诊为成骨不全症的185例先证者进行回顾性分析。
结果
在COL1A1中总共鉴定出140种突变，在COL1A2中鉴定出45种突变，其中18种变异是新的。在表型分析中，中国散发的病例比家族性成骨不全症病例更多（54.6%对45.4%，P < 0.001）。总共98.9%的患者有骨折病史。最常见的骨折部位是四肢长骨（股骨、胫腓骨和尺桡骨分别占36.6%、17.1%和11.7%）。III型和IV型成骨不全症患者，尤其是III型患者，牙本质生成不全（DI）的比例高于I型成骨不全症患者（55%对28%，P < 0.001）。有趣的是，COL1A1中的G767S和D1219N以及COL1A2中的G337S最为常见（分别为3.52%、2.11%和8.89%），它们似乎是中国患者COL1A1和COL1A2基因中的热点突变。
结论
本研究描述了中国成骨不全症主要致病基因COL1A1和COL1A2的突变以及临床特征。此外，这些发现有助于揭示亚洲成骨不全症患者的遗传基础，并有助于遗传咨询。
Introduction Osteogenesis imperfecta (OI) is a well-known heritable disorder of connective tissue characterized by skeletal fragility and low bone mass. Nearly 90% of patients with OI have disease variants inCOL1A1andCOL1A2that encode for the alpha 1 and alpha 2 chains of type I collagen. Materials and methods A retrospective analysis of 185 probands who were diagnosed with OI in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from March 2005 to December 2019 was performed. Results A total of 140 mutations inCOL1A1and 45 mutations inCOL1A2were identified, of which 18 variations were novel. In the phenotype analysis, there were more sporadic cases than familial OI cases in China (54.6% vs. 45.4%,P < 0.001). A total of 98.9% of patients presented with a fracture history. The most common fracture sites were extremity long bones (femur, tibia-fibula and radius-ulna accounted for 36.6%, 17.1% and 11.7%, respectively). Patients with OI types III and IV, especially type III, had a higher proportion of dentinogenesis imperfecta (DI) than patients with OI type I (55% vs. 28%,P < 0.001). Interestingly, G767S and D1219N inCOL1A1and G337S inCOL1A2were the most frequent (3.52%, 2.11% and 8.89%, respectively), which seem to be hotspot mutations in theCOL1A1andCOL1A2genes in Chinese patients. Conclusions This study describes the mutations in the main pathogenic genes,COL1A1andCOL1A2, and the clinical characteristics of osteogenesis imperfecta in China. Furthermore, these findings help reveal the genetic basis of Asian OI patients and contribute to genetic counselling.