Immunohistochemical study of dystrophin in neuromuscular disorders

Dystrophin, a protein product of the gene that is affected in Duchenne/Becker muscular dystrophy (DMD/BMD), is localized on the sarcolemma of muscle fibers. We tried to study various neuromuscular disorders, including DMD/BMD and their carriers, by the immunohistochemical method with two types of anti-dystrophin antibodies. No dystrophin stain was found on the muscles of cases of DMD. In cases of BMD, partial deficiency or a mosaic appearance of dystrophin was found. In members of DMD/BMD families, polyclonal antibody stains did not show definite membrane abnormality. However, partial deficiency or a mosaic appearance of dystrophin on muscle membranes was found in the carriers by a monoclonal anti C-terminal antibody stain. The explanation may be: 1) more non-specific antigen-antibody cross reactions occurred in the polyclonal antibody stain; and 2) a partial defect exists, such as a segmental deletion of the C-terminal portion of dystrophin. Dystrophin study in muscle diseases is a helpful tool for the following reasons: 1) it improves diagnostic accuracy and helps to differentiate variant types of muscle disorders; 2) it makes an early diagnosis possible before the onset of the symptoms of DMD/BMD; and 3) it detects nonsymptomatic carriers of DMD/BMD. However, without the aid of a genetic study, dystrophin antibody stains cannot absolutely rule out the diagnosis of carriers.