Toxic protein linked to muscular dystrophy and arhinia

Friday, February 17, 2023

NIH researchers discover a possible cause for a rare facial malformation, bringing new hope for patients

Researchers at the National Institutes of Health and their colleagues have found that a toxic protein made by the body called DUX4 may be the cause of two very different rare genetic disorders. For patients who have facioscapulohumeral muscular dystrophy (FSHD), or a rare facial malformation called arhinia, this research discovery may eventually lead to therapies that can help people with these rare diseases.

FSHD type 2 (FSHD2) is an inherited form of muscular dystrophy that causes progressive muscle weakness. Arhinia is an extremely rare yet severe disorder that prevents the development of an external nose and the olfactory bulbs and tracts. Both diseases are caused by mutations in the SMCHD1 gene. In patients with FSHD2, there is overproduction of DUX4 which kills the muscle cells, and this leads to the progressive weakening of the muscles.

“It has been known for some time that DUX4 damages the muscle in patients with FSHD2, but what we found is that it can actually also kill the precursors of the human nose,” said Natalie Shaw, M.D., head of the Pediatric Neuroendocrinology Group at the National Institute of Environmental Health Sciences (NIEHS) and lead author of the new study in the journal Science Advances. NIEHS is part of NIH.