Large in-frame deletions of the rod-shaped domain of the dystrophin gene resulting in severe phenotype.

BACKGROUND The prediction that Duchenne muscular dystrophy patients have out-of-frame deletions and Becker muscular dystrophy patients have in-frame deletions of the dystrophin gene holds well in the vast majority of cases. Large in-frame deletions involving the rod domain only have usually been associated with mild (BMD) phenotype. OBJECTIVES To describe unusual cases with large in-frame deletions of the rod-shaped domain of the dystrophin gene associated with severe (Duchenne) clinical phenotype METHODS Screening for dystrophin gene deletion was performed on genomic DNA by using multiplex polymerase chain reaction. Needle muscle biopsies from the quadriceps were obtained using a Bergström needle. The biopsies were stained with histologic and histochemical techniques as well as monoclonal antibodies to dystrophin 1, 2 and 3. RESULTS In three children with large in-frame deletions of the rod domain (exons 10-44, 13-40 and 3-41), early-onset weakness and a disease course suggested the DMD phenotype. CONCLUSIONS This observation emphasizes the uncertainty in predicting the Becker phenotype in a young patient based on laboratory evaluation, and that the clinical picture should always be considered.