Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
Division of Pediatric Endocrinology and Metabolic Bone Diseases, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland; Folkhälsan Institute of Genetics, Helsinki, Finland.
Bone. 2014 Mar;60:246-51. doi: 10.1016/j.bone.2013.12.030. Epub 2013 Dec 31.
The autosomal dominant form of Caffey disease is a largely self-limiting infantile bone disorder characterized by acute inflammation of soft tissues and localized thickening of the underlying bone cortex. It is caused by a recurrent arginine-to-cysteine substitution (R836C) in the α1(I) chain of type I collagen. However, the functional link between this mutation and the underlying pathogenetic mechanisms still remains elusive. Importantly, it remains to be established as to how a point-mutation in type I collagen leads to a cascade of inflammatory events and spatio-temporally limited hyperostotic bone lesions, and how structural and inflammatory components contribute to the different organ-specific manifestations in Caffey disease. In this review we attempt to shed light on these questions based on the current understanding of other mutations in type I collagen, their role in perturbing collagen biogenesis, and consequent effects on cell-cell and cell-matrix interactions.
常染色体显性遗传型 Caffey 病是一种主要呈自限性的婴儿骨疾病，其特征为软组织的急性炎症和骨皮质下局部增厚。它是由Ⅰ型胶原的α1(I)链上的精氨酸到半胱氨酸取代（R836C）引起的。然而，这种突变与潜在的发病机制之间的功能联系仍然难以捉摸。重要的是，仍然需要确定Ⅰ型胶原中的点突变如何导致一连串的炎症事件和时空受限的骨质增生性骨病变，以及结构和炎症成分如何导致 Caffey 病中不同的器官特异性表现。在这篇综述中，我们试图根据对Ⅰ型胶原中其他突变的现有认识、它们在扰乱胶原生物合成中的作用以及对细胞-细胞和细胞-基质相互作用的后续影响来回答这些问题。
