Duchenne phenotype with in-frame deletion removing major portion of dystrophin rod: threshold effect for deletion...

In a 9-year-old boy with Duchenne muscular dystrophy we found a large in-frame deletion, spanning exons 10 to 53 of the dystrophin gene. The deletion removed almost all of the central rod domain of dystrophin. Using carboxyterminal dystrophin antibodies the immunohistochemical reaction was normal in all muscle fibers. In immunoblot studies we found dystrophin of abnormal size (160 kDa) and normal amount (about 100%). The immunochemical features and the reading frame deduced from DNA analysis are usually associated with Becker muscular dystrophy, but the clinical characteristics were those of the severe Duchenne phenotype. All the cases of in-frame dystrophin deletions reported so far, which involved more than 36 exons, invariably resulted in a severe phenotype. Therefore, a threshold effect for dystrophin length may be reasonably suspected. Very short dystrophin molecules might induce a severe disarray of the dystrophin network.