title: Caffey disease: new perspectives on old questions.
abstract: 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.
authors.affiliation: Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
authors.forename: Harikiran
authors.initials: H
authors.lastname: Nistala
authors.affiliation: Division of Pediatric Endocrinology and Metabolic Bone Diseases, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland; Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Mäkitie
authors.affiliation: Pediatric Nephrology Unit and Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: hjueppner@partners.org.
authors.forename: Harald
authors.initials: H
authors.lastname: Jüppner
mesh_terms: D000595:Amino Acid Sequence; D024042:Collagen Type I / Q000737:chemistry / Q000235:genetics; D006801:Humans; D006958:Hyperostosis, Cortical, Congenital / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011859:Radiography
chemical_list: D024042:Collagen Type I
keywords: COX-2; Caffey disease; Collagen; Extracellular matrix; PGE2; TGFβ