Recessive osteogenesis imperfecta: Clinical, radiological, and molecular findings

Abstract

Osteogenesis imperfecta (OI) or "brittle bone disease" is currently best described as a group of hereditary connective tissue disorders related to primary defects in type I procollagen, and to alterations in type I procollagen biosynthesis, both associated with osteoporosis and increased susceptibility to bone fractures. Initially, the autosomal dominant forms of OI, caused by mutations in either COL1A1 or COL1A2, were described. However, for decades, the molecular defect of a small percentage of patients clinically diagnosed with OI has remained elusive. It has been in the last 6 years that the genetic causes of several forms of OI with autosomal recessive inheritance have been characterized. These comprise defects of collagen chaperones, and proteins involved in type I procollagen assembly, processing and maturation, as well as proteins involved in the formation and homeostasis of bone tissue. This article reviews the recently characterized forms of recessive OI, focusing in particular on their clinical and molecular findings, and on their radiological characterisation. Clinical management and treatment of OI in general will be discussed, too.

Novel Deletion of <b><i>SERPINF1</i></b> Causes Autosomal Recessive Osteogenesis Imperfecta Type VI in Two Brazilian Families

“…Sclerae and teeth do not appear to be affected, patients are healthy at birth, and fractures usually occur after 6 months of age [Glorieux et al, 2002;Basel and Steiner, 2009;Homan et al, 2011;Rohrbach et al, 2012]. The pathognomonic histological finding of OI type VI is the large amount of unmineralized osteoid tissue, osteomalacia, and disorganization of the bone matrix where the lamellar pattern is replaced by a fish scale appearance [Homan et al, 2011;Rohrbach et al, 2012]. Radiological findings are non-distinctive in this type of OI and include bowing of long bones, vertebral compression fractures, generalized osteopenia, hyperplastic callus formation, and absence of wormian bones in the majority of cases [Becker et al, 2011].…”

“…In the last few years, the genetic causes of several forms of autosomal recessive OI have been characterized [Rohrbach and Giunta, 2012], and there are currently 10 known genes responsible for these forms of OI. CRTAP (MIM 605497), LEPRE1 (MIM 610339), and PPIB (MIM 123841) encode components of the prolyl 3-hydroxylation complex of P986 in the proalpha1 (I)-collagen chains [Becker et al, 2011;van Dijk et al, 2012].…”

Novel Mutations in FKBP10 and PLOD2 Cause Rare Bruck Syndrome in Chinese Patients

“…Osteogenesis imperfecta (OI) is a remarkably heterogeneous monogenic disease characterized by bone fragility and low bone mass, more than 90% of which are caused by dominant mutations in encoding genes of type I procollagen chains proα1 ( COL1A1 , MIM 120150) or proα2 ( COL1A2 , MIM 120160) [1], [2]. Bruck syndrome (BS, MIM 259450 and 609220) is an extremely rare autosomal recessive form of OI, which is defined by congenital large joint contracture, bone fragility, multiple bone fractures starting in infancy or early childhood [2]–[4].…”

Molecular Consequences of the SERPINH1/HSP47 Mutation in the Dachshund Natural Model of Osteogenesis Imperfecta

“…In ϳ90% of individuals with the clinical diagnosis of OI, dominant mutations in the type I collagen coding genes COL1A1 (Online Mendelian Inheritance in Man (OMIM) 120150) and COL1A2 (OMIM 120160) are responsible for the disorder (1). Over the last 8 years, mutations in several noncollagenous genes involved in the post-translational processing of procollagen I, in osteoblast-specific signaling, or in gene regulation have been characterized in either dominant or recessive forms of OI: CRTAP (OMIM 605497), LEPRE1 (OMIM 610339), PPIB (OMIM 123841), PLOD2 (OMIM 601865), FKBP10 (OMIM 607063), BMP1 (OMIM 112264), CREB3L1 (Entrez ID 90993), IFITM5 (OMIM 614757), PLS3 (OMIM 300131), TMEM38B (OMIM 611236), WNT1 (OMIM 164820), SP7 (OMIM 606633), SERPINF1 (OMIM 172860), SERPINH1 (OMIM 600943) (2), and most recently, P4HB (OMIM 176790) (3) and SEC24D (OMIM 607186) (4).…”