IMMUNOHISTOLOGICAL EVIDENCE FOR 2ND OR SOMATIC MUTATIONS AS THE UNDERLYING CAUSE OF DYSTROPHIN EXPRESSION BY ISOLATED FIBERS IN XP21 MUSCULAR-DYSTROPHY OF DUCHENNE-TYPE SEVERITY

Using five monoclonal antibodies against different parts of the dystro phin molecule, we have studied the dystrophin composition of 17 dystro phin-positive fibres in a muscle biopsy from a boy with Xp21 muscular dystrophy of Duchenne-type severity. The fibres showed five distinct, reproducible, immunoreactive dystrophin profiles. All the profiles inc luded both the N-terminal and the C-terminal domains, but between thes e domains, different fibres were negative for different antibodies, su ggesting the somatic loss of certain exons. We interpret this as the f irst in situ evidence of an individual having different patterns of mi ssing exons leading to restoration of the reading frame in various way s in the original germline frame-shifting deletion of exons 35-43. It follows that various somatic mutations had taken place in different fi bres.