Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation.
Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation.
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DOI：
10.1097/mop.0000000000000117
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发表时间：
2014-08
影响因子：
3.6
通讯作者：
Smith SM
中科院分区：
文献类型：
--
作者：
Marini JC;Reich A;Smith SM
成骨不全症（Osteogenesis imperfecta， OI）或“脆性骨病”，主要被认为是一种由胶原蛋白突变引起的骨骼疾病。然而，在过去的十年中，大量的遗传学发现为OI作为一种胶原相关疾病创造了新的范式，其中常染色体显性I型胶原蛋白缺陷导致大多数病例，而罕见的是，大多数隐性形式是由于蛋白质产物与胶原蛋白相互作用的基因缺陷造成的。这篇综述在概述对成骨不全理解的范式转变的起源、发展和未来方面既及时又相关。BRIL和PEDF缺陷通过骨矿化缺陷导致V型和VI型OI，而CRTAP、P3H1和CyPB缺陷通过胶原翻译后修饰缺陷导致VII-IX型OI。Hsp47和FKBP65缺陷通过异常的胶原交联、折叠和陪伴导致X型和XI型OI，而SP7、WNT1、tricc - b和OASIS缺陷则破坏成骨细胞的发育。最后，I型胶原c -前肽酶BMP1的缺失导致XII型OI，原因是胶原成熟/加工改变。这些多重致病缺陷的识别为准确的遗传咨询提供了重要信息，启发了最近提出的通过共享机制对成骨不全类型进行功能分组，以简化当前的分类学，并应促进对成骨不全常见途径的研究。这样的研究可以产生细胞和骨组织机制的关键信息，并转化为对患者临床治疗的新的机制见解。
Osteogenesis imperfecta (OI), or “brittle bone disease”, has mainly been considered a bone disorder caused by collagen mutations. Within the last decade, however, a surge of genetic discoveries has created a new paradigm for OI as a collagen-related disorder, where autosomal dominant type I collagen defects cause most cases, while rare, mostly recessive forms are due to defects in genes whose protein products interact with collagen protein. This review is both timely and relevant in outlining the genesis, development and future of this paradigm shift in the understanding of OI. BRIL and PEDF defects cause types V and VI OI via defective bone mineralization, while defects in CRTAP, P3H1 and CyPB cause types VII-IX via defective collagen post-translational modification. Hsp47 and FKBP65 defects cause types X and XI OI via aberrant collagen crosslinking, folding and chaperoning, while defects in SP7, WNT1, TRIC-B and OASIS disrupt osteoblast development. Finally, absence of the type I collagen C-propeptidase BMP1 causes type XII OI due to altered collagen maturation/processing. Identification of these multiple causative defects has provided crucial information for accurate genetic counseling, inspired a recently proposed functional grouping of OI types by shared mechanism to simplify current nosology, and should prod investigations into common pathways in OI. Such investigations could yield critical information on cellular and bone tissue mechanisms and translate to new mechanistic insight into clinical therapies for patients.