Mosaic expression of dystrophin in symptomatic carriers of Duchenne's muscular dystrophy.

A deficiency of the protein dystrophin is known to be the cause of Duchenne's muscular dystrophy. To examine the expression of dystrophin in symptomatic female carriers of this X-linked recessive disorder, we performed immunohistochemical studies on muscle-biopsy specimens from three such carriers, using an antiserum raised against a synthetic peptide fragment of dystrophin. In all three carriers, most individual muscle fibers reacted either strongly or not at all to the antiserum for dystrophin; only 2 to 8 percent of fibers showed partial immunostaining. This mosaic staining pattern was present on both cross-sectional and longitudinal muscle specimens. Although the mosaic pattern was seen in all fiber types, more than 80 percent of type 2B and 2C fibers from two of the carriers did not react with the antiserum. Similar studies in nine normal subjects showed consistently strong staining of all muscle fibers. No muscle fibers from 31 patients with Duchenne's muscular dystrophy reacted with the antiserum. We conclude that symptomatic carriers of Duchenne's muscular dystrophy can be identified by a distinct mosaic pattern in the immunohistochemical staining of the surface membrane of skeletal-muscle specimens. This finding may have practical implications for genetic counseling, although it remains to be shown whether the same staining pattern will be found in muscle specimens from asymptomatic carriers of Duchenne's muscular dystrophy.