Rare and painful, a little-known disease known as Hajdu-Cheney syndrome is garnering some attention. Along with colleagues, a researcher from the University of Connecticut (UConn) has discovered the gene that causes Hajdu-Cheney, an affliction that causes the softening—and fracture—of bones.
Using a mouse model, Ernesto Canalis, M.D. and colleagues targeted a gene known as NOTCH2. According to the January 14, 2016 news release, “…this gene has a specific mutation that appears in people with the syndrome.”
As stated in the news release, “His mice seem to provide the answers. They generate a larger pool of osteoclasts, cells that break down and resorb old bone. These cells also mature faster than they do in normal mice. So Hajdu-Cheney mice have far too much bone resorbed by their bodies, and new bone doesn’t grow fast enough to replace it. This leads to mice with fragile bones, very similar to people with the disease.”
“Until now, nobody understood why people afflicted with the disease had osteoporosis and fractures, ” said Dr. Canalis, a professor of orthopedic surgery at UConn Health.
As indicated in the news release, “Hajdu-Cheney is an incredibly rare disease, with fewer than 100 cases ever described. But there are good scientific reasons to study it. It can illuminate the workings of bone formation and destruction, and give insight into a gene important to both the skeleton and the immune system. It could also possibly tell us about Alagille syndrome, another, much more common genetic disease associated with NOTCH2.”
Dr. Canalis told OTW, “We were able to recreate the NOTCH2 mutation found in humans in mice. We were able to establish a mutant mouse colony and studied the skeleton of the mice. We learned that mice with a Hajdu-Cheney mutation exhibited selected aspects of the human disease and developed significant bone loss, at cortical and trabecular sites. We were surprised to learn that the phenotype was due to a higher number of bone resorbing cells that had a greater capacity to differentiate and resorb bone. The results provide a mechanism for the disease and may serve to suggest appropriate therapeutic interventions.”
