An X:Autosome Translocation Stabilizes Truncated Dystrophin: Implications for Lack of Truncated Dystrophins in Duchenne Muscular Dystrophy

Abstract

We report a 5-year-old girl with clinical symptoms of typical Duchenne muscular dystrophy in males. The girl showed dramatic elevations of serum creatine kinase, and muscle biopsy histopathology consistent with a severe dystrophic myopathy. Cytogenetic analysis revealed an X:22 translocation (46,X,t [X;22] [p21.2; 11.2]). Dystrophin immunofluoresence studies showed strong membrane immunostaining of dystrophin with antibodies directed against the amino terminus of the protein, but vastly reduced immunostaining with carboxylterminal antibodies. Immunoblot studies showed a major immunoreactive protein of approximately 350 kDa at approximately 20 % levels. Nested RT-PCR analysis of the dystrophin mRNA in the patient's muscle showed the RNA to be positive for primers covering the first 85 % of the dystrophin coding sequence, and negative for the carboxyl-terminal 15 %. Taken together, our data suggests that the translocation breakpoint occurs towards the 3' end of the gene. The translocated dystrophin gene is still expressed into a truncated dystrophin protein associated with the plasma membrane. Our results are consistent with the translocation resulting in a more stable abnormal dystrophin mRNA.

Key words

DMD, female - X:autosome translocation - Dystrophin