20 Feb NIEHS Study Finds Same Toxic Protein Can Cause Two Rare Genetic Diseases

MedicalResearch.com Interview with:

Dr. Shaw

Natalie Shaw, M.D., MMSc.
Principal Investigator
Head of the Pediatric Neuroendocrinology Group
Dr. Shaw holds a secondary appointment in NIEHS
Reproductive and Developmental Biology Laboratory.

MedicalResearch.com: What is the background for this study? Would you briefly describe the two affected conditions?

Dr. Shaw: Congenital arhinia is a rare congenital malformation characterized by the complete absence of an external nose and internal olfactory (smell) structures.  It is frequently associated with eye and reproductive defects.  Facioscapulohumeral muscular dystrophy (FSHD) type 2 is a form of muscular dystrophy that presents in young adulthood.  Both conditions are caused by mutations in the gene SMCHD1.  In FSHD type 2, we know that loss of SMCHD1 activity leads to expression of a toxic protein called DUX4 in muscle.  The cause of arhinia was unknown.

MedicalResearch.com: What are the main findings?

Dr. Shaw: We found that arhinia, like FSHD type 2, is caused by inappropriate DUX4 expression, but in a different cell type – cranial placode cells.  These are the precursors of the human sensory organs (eyes, nose, etc).

MedicalResearch.com: What should readers take away from your report?

Dr. Shaw: This is the first report, to our knowledge, of a birth defect being caused by a toxic protein made by the body itself.  It is also an example of how studying a rare birth defect can help us understand more common conditions like FSHD.

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Dr. Shaw: Understanding what controls DUX4 expression and what causes DUX4 to be toxic to placode cells may also improve our understanding of DUX4 toxicity in muscle cells in patients with FSHD and potentially lead to new treatments.

Citation:

Kaoru Inoue, Hamed Bostan, MaKenna R. Browne, Owen F. Bevis, Carl D. Bortner, Steven A. Moore, Aaron A. Stence, Negin P. Martin, Shih-Heng Chen, Adam B. Burkholder, Jian-Liang Li, and Natalie D. Shaw. DUX4 double whammy: the transcription factor that causes a rare muscular dystrophy also kills the precursors of the human nose.  Science Advances. DOI: 10.1126/sciadv.abq7744

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Last Updated on February 20, 2023 by Marie Benz