An X:autosome translocation stabilizes truncated dystrophin: implications for lack of truncated dystrophins in Duchenne muscular dystrophy.
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 carboxyl-terminal 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.
D000911:Antibodies, Monoclonal; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22; D016189:Dystrophin / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D009132:Muscles / Q000737:chemistry; D009136:Muscular Dystrophies / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012313:RNA; D014178:Translocation, Genetic; D014960:X Chromosome
D000911:Antibodies, Monoclonal; D016189:Dystrophin; D012313:RNA