Deficiency of brain synaptic dystrophin in human Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is characterized by a defect in dystrophin, a high molecular weight protein that is located predominantly in muscle, but which has been detected in brain. Brain dystrophin has been localized to the synapse, in the postsynaptic density (PSD), and is absent in the mdx mouse, an animal model of human DMD. To define the potential pathogenic role of dystrophin deficiency in cognitive impairment, we examined the protein in human DMD brain. The 427-kd dystrophin was absent in the PSD from DMD brain, but was normally expressed in the brain from an age-matched control subject. Our findings indicate that dystrophin is deficient in human DMD cortical synapses and provide a potential pathogenic mechanism for cognitive impairment.