Caveolin 3 gene and mitochondrial tRNA methionin gene in Duchenne muscular dystrophy

الملخص EN

Background: It was recently reported that Duchene muscular dystrophy (DMD) patients and mdx mice have elevated levels of caveolin-3 expression in their skeletal muscles.

However, it remains unknown whether this increased caveolin-3 levels contribute to the pathogenesis of DMD.

Also mitochondrial DNA mutation in the tRNA methionin (tRNA Met) gene has been shown to be associated with muscle weakness, severe exercise intolerance, lactic acidosis and growth retardation.

Since DMD is X-linked maternally inherited disease, mitochondrial mutation in tRNA (Met) gene can be suspected to be the cause for the inefficient splicing of dystrophin gene during its expression and can be implicated as the cause of dystrophin inactive protein.

Aim of the Work: The aim of the present study is to investigate whether mutations in caveolin gene leads to its increased expression and/or mutation in the tRNA (Met) gene can be associated with DMD pathogenesis.

Patients and Methods: Expression of caveolin mRNA by RT-PCR and mutations in caveolin gene and tRNA (Met) gene were measured in 28 patients presented with DMD symptoms using the single strand conformation polymorphism assay (SSCP).

Results: Results gave further proof to decreased expression of inducible nitric oxide synthase (iNOS) mRNA, which leads to increased expression in caveolin 3 mRNA in lymphocytes of DMD patients compared to controls.

However using SSCP, there was no evidence for tRNA (Met) gene mutation among DMD patients and only one patient presented a mutation in the caveolin gene compared to controls.

Conclusion: There is an inverse relation between iNOS and Caveolin 3 in lymphocytes of DMD patients compared to controls.

However, Caveolin 3 gene mutation is excluded as the main cause of increased caveolin gene expression.

Also, there was no evidence for tRNA (Met) gene mutation among DMD patients.