Abstract
Osteogenesis imperfecta (OI) is an inherited connective tissue disorder characterized by bone fragility and is characterized by clinical and genetic heterogeneity. Previous studies showed that the same mutation (c.−14C> T) of the IFITM5 gene is responsible for autosomal dominant OI type V. However, the mutation has a variable expressivity. Clinical heterogeneity has been recognized in OI type V. In this study, we investigated 13 individuals with molecularly confirmed OI type V from seven Chinese families and explored the genotype-phenotype relationship. Increased callus formation is not observed in all individuals, and several novel clinical features were described: joint contractures (three individuals) and unexplained hip arthritis (six individuals). Significant clinical variability was observed even within families. Specific facial features were observed in six individuals from two families consistent with the facial features associated with OI type V reported so far in the literature. Interestingly, we report the process of hypertrophic callus formation in detail for the first time, and in five individuals with hyperplastic callus, increased erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (C-RP) were measured, suggestive of inflammatory activation.
Highlights
Osteogenesis imperfecta (OI) comprises a heterogeneous group of diseases characterized by susceptibility to bone fractures with variable severity and in most cases presumed or proven defects in collagen type I biosynthesis
Several teams confirmed that OI type V is consistently associated with a unique point mutation (c.-14C>T) in the 5′ untranslated region (UTR) of the IFITM5 gene [2, 3]
This study included children, adults and adolescents who met the diagnostic criteria for OI type V: [1] history of recurrent fracture; [2] hyperplastic callus formation; [3] radiologically apparent calcification of the forearm; [4] no mutation found on COL1A1 or COL1A2 by Sanger sequencing; and [5] other possible diseases were excluded
Summary
Osteogenesis imperfecta (OI) comprises a heterogeneous group of diseases characterized by susceptibility to bone fractures with variable severity and in most cases presumed or proven defects in collagen type I biosynthesis. The main characteristic is a liability to fractures. In 2000, Glorieux et al [1] reported several patients with distinctive clinical manifestations (hyperplastic callus formation [HC], radial head dislocation [RHD], radioulnar interosseous membrane ossification [RUIMO], and limitation in forearm rotation) and characteristic histopathology (irregular arranged lamellae and “mesh-like” appearance under polarized light) as having OI type V. IFITM5 is an osteoblast-specific gene associated with matrix mineralization that plays a putative role in bone formation and osteoblast maturation [4]. As it turns out, the mutation (c.-14C>T) results in five amino acids (Met-Ala-Leu-Glu-Pro)
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