New Gene Discovered for Recessive Form of Brittle Bone Disease
News Jan 22, 2010
Researchers at the National Institutes of Health and other institutions have discovered the third in a sequence of genes that accounts for previously unexplained forms of osteogenesis imperfecta (OI), a genetic condition that weakens bones, results in frequent fractures and is sometimes fatal.
The newly identified gene contains the information needed to make the protein Cyclophilin B. This protein is part of a complex of three proteins that modifies collagen, folding it into a precise molecular configuration, before it is secreted from cells. Collagen functions as molecular scaffolding that holds together bone, tendons, skin and other tissues.
Most types of osteogenesis imperfecta result from a dominant mutation in collagen itself, requiring only one copy of the mutated gene to bring about the disorder. Osteogenesis imperfecta involving the Cyclophilin B gene is a recessive trait, requiring two defective copies of the gene to cause the disorder.
"The discovery provides insight into a previously undescribed form of osteogenesis imperfecta," said Alan E. Guttmacher, M.D., acting director of NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). "The advance also provides new information on how collagen folds during normal bone formation, which may also lead to greater understanding of other bone disorders."
The finding was published online Jan. 20 in the New England Journal of Medicine. The investigation involved a collaboration between researchers at the NICHD, led by Dr. Joan Marini, and the Hospital for Special Surgery in New York City.
There, Dr. Cathleen Raggio diagnosed the children in the study as having a novel form of OI. In addition, researchers at the University of Washington in Seattle and the NIH's National Institute of Human Genome Research also took part in the study.
There are hundreds of thousands of structural variants (SVs) in the human genome that are hard to identify than single nucleotide variants. Researchers have used a full suite of genomic technologies to analyze the number of SVs in three individuals, and the results present as the most comprehensive catalog of SVS to date.READ MORE