Excess Protein Latest Hypothesis on FSHD

An excess of the protein known as mu-crystallin has been identified as a new addition to the array of hypotheses about the molecular basis of facioscapulohumeral muscular dystrophy (FSHD). (See “Impossible Things,”) The researchers noted that the mu-crystallin findings add to and don’t necessarily contradict any of the existing FSHD hypotheses.

MDA grantee Robert Bloch at the University of Maryland School of Medicine and colleagues found much higher levels of the mu-crystallin protein in muscle samples from people with FSHD than from people without a neuromuscular disease or with other forms of muscular dystrophy or inflammatory muscle diseases.

The investigators, who published their results in the June issue of Experimental Neurology, suggest that changes in mu-crystallin may also explain the changes that occur in tissues other than muscle that are affected in FSHD.

Mu-crystallin is found in the retina, and retinal abnormalities affect some FSHD patients. Abnormalities in this protein have also been associated with deafness, and hearing loss sometimes occurs in FSHD.

In addition, mu-crystallin interacts with thyroid hormone, a potent signaling molecule that acts early in muscle cell maturation.

The gene for mu-crystallin is located on chromosome 16, while the only defect known to be associated with the disease is a missing section of DNA on chromosome 4. However, investigators have long suspected that the chromosome 4 deletion may affect the activity of genes far from its location, including on other chromosomes.

Since the publication of this paper, lead author Patrick Reed, also at the University of Maryland, has been awarded an MDA grant to probe this and other protein abnormalities in FSHD.