The Laboratory of Functional Genomics of the Research Centre for Medical Genetics has developed a technology for the analysis of splicing mutations for the accurate diagnosis of Duchenne-Becker muscular dystrophy
Splicing is the process of RNA maturation, in which certain sections of the gene are cut out and those that later become a template for protein synthesis are “sewn together”. Splicing defects can lead to the misfunction of the protein. The protein created on base of the "wrong" template, will not be able to perform its functions in the body, and this will cause serious illness.
Duchenne-Becker muscular dystrophy is one of the most common hereditary diseases caused by mutations in the DMD gene encoding the dystrophin protein. The study of the structure of the gene and its functionality is expensive, it is a complex and lengthy process. At the same time, the analysis of mutations in the gene cannot always give an accurate answer, since not all variants found in DNA diagnostics lead to the disease. In many cases, only additional experiments can determine the pathogenicity of the identified mutation.
Specialists from the Laboratory of Functional Genomics of the Research Centre for Medical Genetics suggested that the first stage of protein synthesis - RNA transcription - should be studied in order to make an accurate diagnosis. This information allows to understand whether the RNA molecule, that serves as a template for the dystrophin protein, is formed correctly. Mutations that lead to changes in splicing, indeed occur in patients with Duchenne-Becker myodystrophy, according to the Laboratory of Functional Genomics of the Research Centre for Medical Genetics, but they are still poorly described and studied.
Specialists from the Laboratory of Functional Genomics of the Research Centre for Medical Genetics have developed a system that includes more than 20 exons of the DMD gene. These sections are included in the mature RNA, which later serves as a template for the synthesis of dystrophin. The system was tested on various mutations to show its effectiveness. The system allows the analysis of nucleotide variants in the DMD gene in both Russian and international patients. Antisense oligonucleotides that block splicing mutations, are used for the treatment of Duchenne-Becker muscular dystrophy. This makes it possible to significantly improve the condition of patients. In Russia, these drugs remain a treatment in prospect.