Functional significance of dystrophin positive fibres in Duchenne muscular dystrophy

Abstract

The age when boys lose the ability to walk independently is one of the milestones in the progression of Duchenne muscular dystrophy (DMD). We have used this as a measure of disease severity in a group of 30 patients with DMD and six patients with intermediate Duchenne/Becker dystrophy (D/BMD). Dystrophin analysis was performed on tissue sections and 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 higher proportion (about 25%). The mean age at loss of mobility among the 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 labelling was 9.9 years (range 8.0-11.9); this is a significant difference. Quantitative estimates of dystrophin abundance were obtained from densitometric analysis of dystrophin bands on blots. In the whole group of 36 patients, a significant positive relationship was found between the abundance of dystrophin and the age at loss of independent mobility. It is concluded that even the very low concentrations of dystrophin found in DMD patients may have some functional significance.