Bone Abstracts

Osteogenesis imperfecta (OI) is usually caused by dominant mutations affecting one of the two genes that code for two collagen type 1, but a recessive form of OI is present in 5–10% of individuals with a clinical diagnosis of OI. Most of the involved genes code for proteins that play a role in the processing of collagen type 1 protein (BMP1, CREB3L1, CRTAP, LEPRE1, P4HB, PPIB, FKBP10, SERPINF1, SERPINH1, PLOD2, SEC24D, and TMEM38B), or interfere with osteoblast function (LRP5, SP7, and WNT1). Mutations in these genes usually lead to severe recessive OI that on clinical evaluation is often difficult to distinguish from OI caused by dominant mutations. However, specific phenotypes are caused by mutations in SERPINF1 (recessive OI type VI), P4HB (Cole-Carpenter syndrome) and SEC24D (‘Cole-Carpenter like’). For most of these new gene defects the mechanisms linking mutation to phenotype remain to be elucidated. Thus, over the past decade, at least 15 genes have been associated with recessive OI.

Disclosure: Receipt of grants/research support: Novartis, Alexion; receipt of honoraria or consultation fees: Genzyme.