Six Novel Transcripts That Remove a Huge Intron Ranging from 250 to 800 kb Are Produced by Alternative Splicing of the 5′ Region of the Dystrophin Gene in Human Skeletal Muscle

The dystrophin gene, which is mutated in patients with Duchenne and Becker muscular dystrophies, comprises 79 exons and is thus the largest known human gene. A full spectrum of splicing of dystrophin transcript has not been elucidated yet. In this study, 6 novel alternative splicing reactions were discovered in the 5′ region by amplifying the cDNA corresponding to exons M1 through 18. Two of these novel transcripts maintain the translational reading frame and are presumed to produce truncated dystrophin, while the other four have disrupted reading frames. The physical distance between splice donor and acceptor sites ranged from 250 kb to 800 kb. Furthermore, the same six alternative splicing products were obtained from mouse skeletal muscle cDNA. This indicated that these novel alternative splicing events are conserved in humans and mice.