© 1993 Oxford University Press
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Characterization of translational frame exception patients in Duchenne/Becker muscular dystrophy
1Departments of Medical Biochemistry, College of Medicine, Ohio State University Means Hall, Room 452, 1654 Upham Drive, Columbus, OH 43210, USA 2Departments of Neurology, College of Medicine, Ohio State University Means Hall, Room 452, 1654 Upham Drive, Columbus, OH 43210, USA 3Departments of Pathology, College of Medicine, Ohio State University Means Hall, Room 452, 1654 Upham Drive, Columbus, OH 43210, USA 4Department of Molecular Genetics, College of Biological Sciences, Ohio State University Means Hall, Room 452, 1654 Upham Drive, Columbus, OH 43210, USA 5Department of Genetics, Hospital for Sick Children, 555 University Avenue Toronto, Ontario M5G 1X8, Canada 6Department of Neurology, University of Rochester and Strong Memorial Hospital, 601 Elmwood Avenue Rochester, NY 14620, USA
* To whom correspondence should be addressed at: Department of Neurology, 452 Means Hall, 1654 Upham Drive, Ohio State University, Columbus, OH 43210, USA
Received February 3, 1993; Revised March 31, 1993; Accepted March 31, 1993
The clinical progression of Duchenne muscular dystrophy (DMD) patients with deletions can be predicted in 93% of cases by whether the deletion maintains or disrupts the translational reading frame (frameshift hypothesis). We have identified and studied a number of patients who have deletions that do not conform to the translational frame hypothesis. The most common exception to the frameshift hypothesis is the deletion of exons 3 to 7 which disrupts the translational reading frame. We identified a Becker muscular dystrophy (BMD) patient, an intermediate, and a DMD patient with this deletion. In all three cases, dystrophin was detected and localized to the membrane. One DMD patient with an inframe deletion of exons 4–18 produced no dystrophin. One patient with a mild intermediate phenotype and a deletion of exon 45, which shifts the reading frame, produced no dystrophin. Two patients with large inframe deletions had discordant phenotypes (exons 3–41, DMD; exons 13–48, BMD), but both produced dystrophin that localized to the sarcolemma. The DMD patient, 113, indicates that dystrophin with an intact carboxy terminus can be produced in Duchenne patients at levels equivalent to some Beckers. The dystrophin analysis from these patients, together with patients reported in the literature, indicate that more than one domain can localize dystrophin to the sarcolemma. Lastely, the data shows that although most patients show correlation of clinical severity to molecular data, there are rare patients which do not conform.
+ These authors contributed equally to this work
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