Is the maintainance of the C-terminus domain of dystrophin enough to ensure a milder Becker muscular dystrophy phenotype?

The severe Duchenne muscular dystrophy (DMD) and the more benign Becker type (BMD) are allelic conditions, controlled by a defective gene at Xp21, caused by the absence (DMD) or a defect in quantity or quality (BMD) of the protein dystrophin. It has been suggested that the C-terminus domain of dystrophin is fundamental to ensure the proper protein sub-cellular localization and function. We wish to report our dystrophin findings in 4 among 142 DMD patients studied for DNA deletions and dystrophin analysis. Although they have a severe clinical course, a positive dystrophin immunofluorescence pattern was seen using C-terminal antibody, and a dystrophin band of reduced molecular weight (corresponding to their DNA deletions), but which maintained the C-terminus was seen through Western blot (WB). Based on these findings, we suggest that in order to partially maintain its function, resulting in a milder phenotype, dystrophin may carry large internal deletions but in addition to the C-terminus, the region encompassing both the N-terminus and the proximal region of the rod domain cannot be absent. Therefore, the prognosis of a Becker phenotype in a young patient should be done with caution if based only on the presence or not of dystrophin.