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.
An X:autosome translocation stabilizes truncated dystrophin: implications for lack of truncated dystrophins in Duchenne muscular dystrophy / A. MORRONE; E. PEGORARO; E. ZAMMARCHI; E. HOFFMAN; A. FIDZIANSKA; B. RYNIEWICZ; A. ILNICKA. - In: NEUROPEDIATRICS. - ISSN 0174-304X. - STAMPA. - 26:(1995), pp. 163-167. [10.1055/s-2007-979747]
An X:autosome translocation stabilizes truncated dystrophin: implications for lack of truncated dystrophins in Duchenne muscular dystrophy.
MORRONE, AMELIA;ZAMMARCHI, ENRICO;
1995
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 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.File | Dimensione | Formato | |
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Fidzianska et al 1995 Neuroped.pdf
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