Scientists have identified a new form of the bone disorder osteogenesis imperfecta, and have determined the genetic defect that underlies it, according to a study to be published in the March 2007 issue of Nature Genetics. Osteogenesis imperfecta (OI) is a disorder characterized by bones that break easily, and is caused by mutations in the gene encoding the protein type I collagen. The classical form of OI is a dominant disease, meaning that a mutation in only one copy of the type I collagen gene is sufficient to cause the disease.
Joan Marini and colleagues have now identified a new recessive form of the disease, in which mutations of both copies of a gene are required. Predicting that some forms of OI might be caused by altered forms of proteins that interact with and modify type I collagen, the authors sequenced the gene encoding an enzyme called P3H1 in five individuals with severe or lethal abnormal bone development. Mutations that either significantly reduced or eliminated the amount of P3H1 were found in all five individuals. P3H1 chemically modifies a single amino acid in type I collagen, which presumably facilitates folding and promotes stability. This recessive form of OI has features that overlap with those of classical OI, but is also characterized by distinctive features.
Joan Marini (National Institute of Child Health and Human Development, Bethesda, MD, USA)
Abstract available online.
(C) Nature Genetics press release.
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