Melorheostosis: Exome sequencing of an associated dermatosis
implicates postzygotic mosaicism of mutated KRAS
Melorheostosis is called a “dysostosis” by physicians. This translates to some type of abnormality of the development and shaping of one or a few bones within the skeleton. A dysostosis differs from a skeletal “dysplasia” where some type of left/right symmetrical abnormality of bone shaping is present in the skeleton. In dysplasias, a genetic abnormality is shared by all cells in the body following conception. The asymmetrical nature of melorheostosis led researchers to, in contrast, suspect that during development fetuses destined to show melorheostosis acquired a DNA mutation replicated into only the cells that would become melorheostotic bone.
This year, 2017, Dr. Whyte and colleagues in St. Louis, MO fully published their study that aimed to determine the cause and mechanism for melorheostosis. They investigated the DNA of a young man with characteristic skin changes that often overlie melorheostosis bone. Such skin changes for many years have been considered a clue to what has gone wrong within the melorheostosis skeleton. They used samples of the patient’s abnormal and normal skin and blood to see if there was a DNA mutation in the abnormal skin that might be causing melorheostosis. They discovered exclusively in the abnormal skin a single DNA change (mutation) affecting one of the two copies each of us has in our KRAS gene. Thinking that this genetic defect would likely also be present deeper in the melorheostosis skeleton, here was a potential clue from one patient.
Accordingly, this approach to studying melorheostosis is now in the medical literature, hoping that other researchers with melorheostosis patients can use their experience as a guide to how to determine the etiology (cause) and pathogenesis (mechanism) for melorheostosis. This publication can be accessed at the following link (DOI: 10.1016/j.bone.2017.04.010) courtesy of Dr. Sundeep Khosla at the Mayo Clinic who is Editor of the medical journal Bone published by Elsevier.
Michael P. Whyte, M.D.
© Copyright 2001—2022 Melorheostosis Association. All rights reserved.