Spectrum of Severity Suggested In
Myopathies With Central Nuclei

Mice bred without genes for the protein known as gamma-actin develop a muscle disease that resembles human centronuclear myopathy (CNM), a muscle disorder characterized by weakness and misplacement of cell nuclei toward the center of the fiber, according to researchers at the University of Wisconsin and the University of Maryland. In humans, the gamma-actin gene is located on chromosome 17.

Researchers coordinated by MDA grantee James Ervasti, now at the University of Minnesota-Twin Cities (although he performed this work while at the University of Wisconsin-Madison) published their findings in the September issue of Developmental Cell.

The findings may add to the diversity of genetic mutations and protein abnormalities that underlie CNM, which, until recently, was considered to be synonymous with myotubular myopathy (MTM), so named in the 1960s because the muscle fibers’ appearance superficially resembles that of immature fibers called myotubes.

In 1997, mutations in the gene for myotubularin, on the X chromosome, were identified as the underlying problem in MTM, now generally thought of as a severe form of CNM.

Last year, a team that included Alan Beggs, an MDA research grantee at Children’s Hospital in Boston, identified mutations in the gene for dynamin 2, on chromosome 19, as a cause of dominantly inherited (only one gene mutation can produce disease symptoms) CNM. This form of the disease is generally somewhat milder than the X-linked, myotubularin-related form.

So far, no human patients with gamma-actin-related CNM have been identified, although Ervasti and colleagues write that their findings “support the screening of genetically undiagnosed patients for [gamma-actin] mutations.”