The known Duchenne muscular dystrophy (DMD) gene products, the muscle-and brain-type dystrophin isoforms, are 427-kDa proteins translated from 14-kilobase (kb) mRNAs. Recently we described a 6.5-kb mRNA that also is transcribed from the DMD gene. Cloning and in vitro transcription and translation of the entire coding region show that the 6.5-kb mRNA encodes a 70.8-kDa protein that is a major product of the DMD gene. It contains the C-terminal and the cysteine-rich domains of dystrophin, seven additional amino acids at the N terminus, and some modifications formed by alternative splicing in the C-terminal domain. It lacks the entire large domain of spectrin-like repeats and the actinbinding N-terminal domain of dystrophin. This protein is the major DMD gene product in brain and other nonmuscle tissues but is undetectable in skeletal muscle extracts.

Palyelanal (DMD) patients and rndjc mice through mutations which disrupt the reading frame of the transcript preventing dystrophin expression in the corresponding skeletal muscles [g-14]. I-Iigh concentrations of dystrophin (or a dyscrophin-like protein) have been observed at the neuromuscular junctions (NMJ) in normal rats, rabbits or mice as well as in the electric organ of Torpedo marmwata recently reported a positive immunofluorescence response at the NMJ of DMD patients and rndx mice, using antibodies raised against the central and distal parts of chicken skeletal muscle dystrophin [20,21].We now observe a protein of Mr 400000 which is present in extracts of mdx muscle from regions which contain NMJs and is absent from those which do not. This NMJ-associated homologue of dystrophin has at least 2 epitopes which are different to the usual Xp21 form of dystrophin expressed along the sarcolcmma of muscle fibres in normal muscles. This protein is also expressed at the NMJ of a DMD patient who lacks the first 52 exons of the Xp21 dystrophin gene. MATERIALS AND METI-IODS Biopsy tnarerials and diagnosesThe patient was a g-year-old male who has followed a severe, Duchcnne course and is also mentally retarded. No hybridization