FUNCTIONAL-SIGNIFICANCE OF DYSTROPHIN POSITIVE FIBERS IN DUCHENNE MUSCULAR-DYSTROPHY

The age when boys lose the ability to walk independently is one of the milestones in the progression of Duchenne muscular dystrophy (DMD). W e have used this as a measure of disease severity in a group of 30 pat ients with DMD and six patients with intermediate Duchenne/Becker dyst rophy (D/BMD). Dystrophin analysis was performed on tissue sections an d western blots of muscle biopsy specimens from these patients and the relationships that were found between clinical severity and abundance of dystrophin labelling are reported. All patients with intermediate D/BMD had dystrophin labelling that was detected on sections and blots . Weak dystrophin labelling was found in sections from 21/30 DMD cases and on blots in 18/30 cases. Two non-exclusive patterns of dystrophin labelling were observed on sections: very clear labelling on a small percentage of fibres (usually <1%) or very weak labelling on a much hi gher proportion (about 25%). The mean age at loss of mobility among th e DMD patients with no dystrophin labelling on tissue sections was 7.9 years (range 6.3-9.5) while the mean age among those with some labell ing was 9.9 years (range 8.0-11.9); this is a significant difference. Quantitative estimates of dystrophin abundance were obtained from dens itometric analysis of dystrophin bands on blots. In the whole group of 36 patients, a significant positive relationship was found between th e abundance of dystrophin and the age at loss of independent mobility. It is concluded that even the very low concentrations of dystrophin f ound in DMD patients may have some functional significance.