April 16, 2018Rare Diseases
"Dripping candle wax" bone disease, is a very rare disorder known as melorheostosis, that causes excess bone formation that resembles dripping candle wax on x-rays. The condition causes pain and bone deformity, which can limit the function of bones. Although there are only about 400 known cases of this disorder worldwide, 15 unrelated adults with the condition from around the globe volunteered to come to the NIH Clinical Center to undergo biopsies of both affected and unaffected bones.in order to uncover a genetic basis of their bone disease. The results, appearing in Nature Communications (11 April 2018), offer potential treatment targets for this rare disease, provide important clues about bone development, and may lead to insights about fracture healing and osteoporosis.
The authors compared samples of healthy and affected bone from each participant to look for differences in the exome, the portion of the genome that codes for proteins. By comparing genetic information from both samples in each patient allowed the team to pinpoint even low levels of the mutations. The analysis revealed that 8 of the 15 participants had mutations in the MAP2K1 gene in the affected bone only. MAP2K1 produces the protein MEK1. The gene MAP2K1 has previously been linked to some types of cancerous growths as well as to conditions that lead to abnormal blood vessel formation in the head, face or neck. In melorheostosis, all the identified MAP2K1 mutations affected a region of the MEK1 protein that normally suppresses its activity, thus they cause MEK1 to become overactive. The bone growth is considered benign and does not spread to other parts of the body.
According to the authors, 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. The authors added that 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 reasoning is that while most adults have the problem of weakening bones as they grow older, these patients have the opposite problem as some of their bones are rock hard and still growing.