Osteogenesis Imperfecta – Diagnosis

T1 - Production of overmodified type I procollagen in a case of osteogenesis imperfecta

Osteogenesis Imperfecta | Collagen | Bone

AB - Skeletal deformity and bone fragility are the hallmarks of the brittle bone dysplasia osteogenesis imperfecta. The diagnosis of osteogenesis imperfecta usually depends on family history and clinical presentation characterized by a fracture (or fractures) during the prenatal period, at birth or in early childhood; genetic tests can confirm diagnosis. Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure. In the past decade, (mostly) recessive, dominant and X-linked defects in a wide variety of genes encoding proteins involved in type I collagen synthesis, processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells have been shown to cause osteogenesis imperfecta. The large number of causative genes has complicated the classic classification of the disease, and although a new genetic classification system is widely used, it is still debated. Phenotypic manifestations in many organs, in addition to bone, are reported, such as abnormalities in the cardiovascular and pulmonary systems, skin fragility, muscle weakness, hearing loss and dentinogenesis imperfecta. Management involves surgical and medical treatment of skeletal abnormalities, and treatment of other complications. More innovative approaches based on gene and cell therapy, and signalling pathway alterations, are under investigation.

Osteogenesis imperfecta is an hereditary defect in the synthesis of collagen fibres.

Osteogenesis imperfecta - collagen synthesis - YouTube

Christiansen HE et al. Homozygosity for a missense mutation in SERPINH1, which encodes the collagen chaperone protein HSP47, results in severe recessive osteogenesis imperfecta. Am J Hum Genet 2010 Mar 12;86(3):389-98.

Alanay Y et al “American journal of human genetics.” Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am J Hum Genet 2010 Apr 9;86(4):551-9.


Osteogenesis imperfecta: Clinical features and diagnosis

Byers PH et al. Perinatal lethal osteogenesis imperfecta (OI type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen. Am J Hum Genet. 1988 Feb;42(2):237-48.

20/01/2012 · Osteogenesis imperfecta ..

Wenstrup RJ et al. Distinct biochemical phenotypes predict clinical severity in nonlethal variants of osteogenesis imperfecta. Am J Hum Genet. 1990 May;46(5):975-82.

24/05/2010 · Osteogenesis imperfecta ..


Osteogenesis imperfecta in childhood: cardiac and renal manifestations.
Vetter U, Maierhofer B, Muller M, Lang D, Teller WM, Brenner R, Frohneberg D, Worsdorfer O.

Osteogenesis imperfecta: Practical treatment guidelines

A successful aortic valve replacement in a patient with type I osteogenesis imperfecta is described with special reference to hematologic manipulations to control bleeding post-operatively.

The differential diagnosis of osteogenesis imperfecta tarda ..

Additional clinical manifestations such as blue sclerae, dentinogenesis imperfecta, joint laxity, and maturity onset deafness are described in the literature.

Osteogenesis Imperfecta – Collagen defect - USF Health

For instance, spontaneous mutations resulting in non- functional α2 chains and formation of type I homotrimers cause severe bone pathology (osteogenesis imperfecta) in humans and in animals.

Osteogenesis Imperfecta – Collagen defect

Shaheen R et al. Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation. J Med Genet 2012 49:630-635.