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The Genetics of Osteogenesis Imperfecta Type III

written by: bjlbyron•edited by: Leigh A. Zaykoski•updated: 6/30/2011

Osteogenesis imperfecta type III is a rare, but highly debilitating, genetic disorder that is marked by fairly severe bone defects. Read on to learn about this condition, what is known about its underlying genetic causes and what is being done to develop a method of treating it.

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    What Is OI Type III?

    Osteogenesis imperfecta (OI) type III is a genetic condition in which affected individuals suffer from a number of bone problems. These problems include:

    • Brittle bones that break easily, even when under conditions of low stress
    • Shortened bones (which can result in reduced height of the affected individual)
    • Loose joints that are prone to injury
    • Abnormally shaped rib cage
    • Curved spine
    • Brittle teeth
    • Abnormal development of the small bones of the ear, a defect which often causes hearing loss

    It is estimated that about 20,000-50,000 people in the United States suffer from one of the six forms of OI, which makes OI a fairly prevalent genetic disorder. The Type III form of OI is a moderate form of OI (two forms are milder and three forms are more severe), but it is still rather debilitating to those who suffer from it.

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    What Is Known About The Genetics Of OI Type III?

    Molecular geneticists have determined that the six forms of OI, collectively, are caused by mutations in four genes, which are referred to as COL1A1, COL1A2, CRTAP and LEPRE1. However, the genes that are mutated in almost all OI Type III cases are the COL1A1 and COL1A2 genes. These two genes encode proteins that each serve a different role in forming type I collagen, which is present in high amounts in bone and skin and which serves to provide structure and strength to the body.

    Interestingly, OI Type III can be inherited in either an autosomal dominant or autosomal recessive manner, as there are several known dominant mutations and there are a few known recessive mutations. In any event, mutation of the COL1A1 gene either leads to no, or a defective form, of COLA1 being made, with the ultimate consequence of insufficient synethesis of type I collagen.

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    Development of Treatment Methods

    Due to the often severe defects that are characteristic of OI Type III, researchers are working hard to develop a method of effectively treating, if not curing, this condition. In one promising case, scientists have successfully disrupted a dominant copy of the COL1A1 gene in human stem cells. It is believed that these cells could be implanted into the bone marrow of individuals who have a dominant allele of the COL1A1 gene to reverse the negative effects of OI Type III. It is likely, however, that researchers will need to show that such treatment is safe and effective in an animal model, such as mouse, before human stem cell treatment will be tested.

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    Genetics Home Reference, National Institutes of Health, Osteogenesis Imperfecta:

    J.R. Chamberlain et al., Gene targeting in stem cells from individuals with osteogenesis imperfecta, Science (2004).

    National Center for Biotechnology Information, Osteogenesis Imperfecta, Type III:

    Osteogenesis Imperfecta Foundation, Fast Facts on Osteogenesis Imperfecta: