成骨不全的基因学研究进展  

Research Advances in Genetic on Osteogenesis Imperfecta

作　　者：袁嘉欣 舒梦 时瀛洲 王姗姗 徐潮[4] 

机构地区：[1]山东大学齐鲁医学院,山东 济南 [2]山东大学第二医院疼痛科,山东 济南 [3]山东第一医科大学临床医学院,山东 济南 [4]山东省立医院内分泌与代谢病科,山东 济南

出　　处：《临床医学进展》2023年第6期9417-9425,共9页Advances in Clinical Medicine

摘　　要：成骨不全症(OI)是一种罕见的遗传性结缔组织疾病,其严重程度广泛,以骨骼畸形和增加的骨脆性为主要特征。其他症状可能会包括侏儒症、脊柱侧弯、牙质发生不全症、耳聋和巩膜泛蓝变色的影响。它以前被认为是由细胞外基质的主要蛋白质I型胶原的缺陷引起的,现在也被认为是一种胶原相关的疾病,由胶原折叠、翻译后修饰和加工缺陷、成骨细胞分化异常和骨矿化引起,OI类型的遗传方式包括常染色体显性和隐性以及X连锁隐性。最常见的OI是由两种I型胶原基因突变(COL1A1, COL1A2)引起的。停止突变通常导致胶原蛋白量减少,导致轻度表型,而错义突变主要引起胶原蛋白的结构改变,导致更严重的表型。在过去的十年中,已经发现了许多其他的致病基因,它们参与了胶原蛋白的生物合成、修饰和分泌、成骨细胞的分化和功能,以及骨稳态的维持。本文章提供了对OI致病基因研究的最新进展。从基因突变对胶原折叠、翻译后修饰和加工、成骨细胞分化和骨矿化等不同过程的影响,综述了20余个与OI相关的致病基因。Osteogenesis imperfecta (OI) is a rare hereditary connective tissue disorder that has a wide range of severity and is characterized by bone deformities and increased bone fragility. Other symptoms may include dwarfism, scoliosis, dental insufficiency, deafness, and the effect of bluish discoloration of the sclera. Previously thought to be caused by a defect in type I collagen, the main protein of the extracellular matrix, it is now also recognized as a collagen-related disease caused by defects in col-lagen folding, post-translational modification and processing, abnormal osteoblastic differentiation and bone mineralization. OI types are inherited in ways that include autosomal dominant and re-cessive as well as X-linked recessive. The most common OI is caused by mutations in two types of collagen I genes (COL1A1 and COL1A2). Stopping mutations usually results in reduced collagen volume, resulting in a mild phenotype, whereas mis-sense mutations mainly cause structural changes in collagen, resulting in a more severe phenotype. Over the past decade, many other dis-ease-causing genes have been identified that are involved in the biosynthesis, modification and se-cretion of collagen, differentiation and function of osteoblasts, and maintenance of bone homeosta-sis. This article provides the latest progress in the study of OI pathogenic genes. In this paper, more than 20 pathogenic genes related to OI are reviewed from the effects of gene mutations on different processes such as collagen folding, post-translational modification and processing, osteoblast dif-ferentiation and bone mineralization.

关 键 词：成骨不全 基因突变 胶原蛋白 骨矿化 成骨细胞 

分 类 号：R73[医药卫生—肿瘤]