(CN) – Working with 15 adults whose bones appear in X-rays to be melting like wax candles, National Institutes of Health researchers reported Wednesday that there is a genetic basis for the rare disorder.
The NIH notes that there are only about 400 known cases of melorheostosis, the official name for the condition marked by excess bone formations that can be both painful and movement limiting.
“Scientists previously assumed that the genetic mutations responsible for melorheostosis occurred in all cells of a person with the disorder,” Dr. Timothy Bhattacharyya at the NIH said in a statement. “Our team hypothesized that mutations might only occur in the affected bone tissue.”
To test out the theory, the NIH performed biopsies at its Clinical Center in Bethesda, Maryland, on 15 individuals with the condition.
The volunteers hailed from around the world, and both affected and unaffected bones were tested.
While eight of the 15 participants in the study had mutations in the MAP2K1 gene in the affected bone only, the researchers found that all of the identified MAP2K1 mutations affected the same part of the protein MEK1 produced by the gene.
This protein region normally suppresses its activity, but the mutation caused MEK1 to become overactive.
The researchers say that MAP2K1 has previously been linked to some types of cancerous growths, and that the comparison of both affected and unaffected bones from the 15 patient samples made it possible for researchers to identify even low levels of the mutations.
Armed with these results, the NIH says it has uncovered important clues about bone development and will allow researchers to develop potential treatment targets, while also learning more about fracture healing and osteoporosis.
Bhattacharyya, the co-senior author of the study, heads up the Clinical and Investigative Orthopaedics Surgery Unit at the National Institute on Arthritis and Musculoskeletal and Skin Diseases at NIH.
“Most adults have the problem of weakening bones as they grow older,” Bhattacharyya said in a statement. These patients have the opposite problem as some of their bones are rock hard and still growing. The prospect that we could somehow harness this pathway in the future is so exciting.”
Bhattacharyya co-authored the study with Dr. Joan Marini, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
“This is an exciting study of a very rare bone disorder that not only identified the responsible mutation in half of the patients, but uncovered fundamental information about the role of a cancer-related gene in the metabolic pathways of normal bone,” Marini said in a statement. “When we started, we had no preconceived causative pathways, but the participation of the patients has really changed the scientific landscape on this topic. Further studies on how this pathway works in both normal and mutant bone cells may have broad implications that could benefit a wider population.”
The Ludwig Boltzmann Institute of Osteology in Austria also worked with the NIH on the study, which was supported by the NIH Intramural Research Program and the Melorheostosis Association.