Bethesda, Md.—Researchers at Suburban Hospital recently published a study in Nature Communications that sheds light on the cause of a rare condition known as "dripping candle wax" bone disease.
This disease, with only about 400 known cases worldwide, is known as melorheostosis and causes the bone lesions as well as the surrounding skin and soft tissue to harden, resembling dripping candle wax on x-rays. This condition causes pain and bone deformity and can limit the function of bones. In this study, 15 patients from around the world were recruited in the hopes of confirming a genetic basis for melorheostosis.
"Many scientists had previously suspected a genetic origin for the disease and that the genetic mutations were present in all the cells of those afflicted with the disease," said co-senior author Timothy Bhattacharyya, M.D., a physician at Suburban Hospital and head of the clinical and investigative orthopaedics surgery unit at the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health (NIH). "However, our team hypothesized that mutations might only occur in the affected bone tissue."
Researchers compared samples of healthy and affected bone from each study participant to look for differences in the protein coding part of the genome, or exome. By comparing genetic information from both samples in each patient, the team was able to identify even low levels of the mutations.
The resulting analysis revealed that 8 of the 15 participants had mutations in the MAP2K1 gene, which produces the protein MEK1, in the affected bone only. In melorheostosis, all the identified MAP2K1 mutations affect a region of the MEK1 protein that normally suppresses its activity, causing MEK1 to become overactive.
The results of the study, according to the researchers, may help in finding a treatment for this disease and add to our understanding about bone development as well as other bone disorders.
"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," said Bhattacharyya. "The prospect that we could somehow harness this pathway in the future is an exciting breakthrough."
The study was supported by the NIH Intramural Research Program (ZIDAR041180 and Z1AHD000408) and the Melorheostosis Association.
The study is registered at ClinicalTrials.gov as NCT02504879.
About Suburban Hospital
Suburban Hospital, a member of Johns Hopkins Medicine, is a community-based, not-for-profit hospital serving Montgomery County and the surrounding area since 1943. The hospital is a regional trauma center with centers of excellence in cardiovascular care, stroke and neurosciences, orthopaedics and oncology. Suburban Hospital’s unique affiliation with the National Institutes of Health, located across the street from the hospital, has brought world-class research from the laboratory to the bedside, providing the local community with around-the-clock access to the most advanced diagnostic and treatment protocols for stroke, heart attack and other clinical conditions. Learn more.
About the National Institutes of Health (NIH)
NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov. The mission of the NIAMS, a part NIH, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about the NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website.