Chapter 15 - FKBP10 (FKBP65 Protein), Osteogenesis Imperfecta and Bruck Syndrome

Abstract

Bruck syndrome (BS) is an autosomal recessive disorder which has skeletal features related to osteogenesis imperfecta (OI) and has traditionally been classified as an OI variant. A characteristic feature of Bruck syndrome is the presence of multiple joint contractures that are congenital and the cause of functional impairment in many patients. Bruck syndrome is a rare cause of bone disease, even within the OI category, perhaps accounting for 1% of the OI population. Bruck syndrome 1 (BS1) is localized to chromosome 17q21.2 and results from mutations in the molecular chaperone, FKBP65. Mutations in FKBP65 also produce moderate to severe OI without contractures. Bruck syndrome 2 (BS2) localizes to chromosome 3 and is due to mutations in PLOD2, which encodes the telopeptide lysyl hydroxylase 2 (LH2). Both proteins have been shown to be involved in the crosslinking of telopeptides in type I collagen. Treatment response data to bisphosphonates is limited in Bruck patients compared to OI patients with type I collagen mutations, but has been used.