Genetic Mutation Causes High Bone Density

Researchers have discovered a genetic mutation that causes extremely high bone density in humans. The finding may suggest a new route for developing drugs that can increase bone density to prevent or treat osteoporosis. The study was published in the May 16, 2002, issue of The New England Journal of Medicine.

The investigators identified a US family with very strong bones because of a genetic mutation. Family members with this mutation have no symptoms, but they do have a strikingly deep and wide jaw and bony growth on the palate. Twenty family members aided the research by providing blood samples for DNA and bone density testing. Seven members of the family had extremely high bone density, while nine had entirely normal density. Serum and urinary biochemical measurements were performed in four members and then compared with results from nine control subjects.

"What we found is that the high bone density in this family behaved as a single gene disorder,” said Richard Lifton, M.D., chair of the department of genetics at Yale School of Medicine (New Haven, CT, USA). "We then went on to map the location of the gene and identified the specific mutation responsible for the high bone density.”

The researchers mapped the gene to the same chromosome segment in LRP5, shown to be the source of a mutation that causes a loss in the function of the LRP5 gene, resulting in low bone density. "It made us wonder if a different mutation increased LRP5 function leading to an opposite phenotype, that is, high bone density,” explained Dr. Lifton. He noted that the study also showed that prevention of the normal inhibition of LRP5 by Dkk, another developmental protein, causes high bone density without other clinical side effects, suggesting a new route for osteoporosis therapy.




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