200 patients with a rare genetic disease tuberous sclerosis were identified at the Research Centre for Medical Genetics
A diagnostic program for tuberous sclerosis has been launched at the Research Centre for Medical Genetics at the beginning of 2022. During the first 5 months of the program, 200 patients with this disease were identified.
Vladimir Strelnikov, Head of the Laboratory of Epigenetics of the Research Centre for Medical Genetics, Doctor of Biological Sciences: “Thanks to the all-Russian diagnostic program, the awareness of doctors about tuberous sclerosis has increased. Now patients with suspected disease are referred for DNA diagnostics. In 2021, only 53 patients underwent a molecular genetic study, comparing to more than 200 patients in 2022. Previously, patients and their families had to solve the problem of further diagnostics on their own. For the majority it was practically inaccessible, and it is not only because of the high analysis costs. The main reason is that family members do not have the necessary knowledge on basic medical issues: which laboratory can make the molecular genetic testing, how to properly store blood for the testing and how to deliver it to the federal center. Now a biomaterial logistics system has been built, and the study is free for patients and medical institutions. Thus, the program has made the diagnosis of tuberous sclerosis available to patients throughout Russia.”
Tuberous sclerosis belongs to the group of rare (orphan) diseases, and its detection presents certain difficulties.
Marina Dorofeeva, neurologist-epileptologist, Doctor of the Highest Category, leading researcher of the department of psychoneurology and epileptology of Veltischev Research and Clinical Institute for Pediatrics of Pirogov Russian National Research Medical University, Head of the Federal Center for Phakomatosis, President of the Interregional Charitable Public Foundation for Patients with Epilepsy ” Sodruzhestvo”, Doctor of Medical Sciences: “Tuberous sclerosis is a multisystem disease, which means that patients can be followed by doctors of different specialties: neurologists, cardiologists, pediatricians. Tuberous sclerosis occurs in 1 in 10,000 people. It is one of the most common orphan diseases. It is extremely important to make a correct diagnosis in time, for patients to receive effective life-saving therapy. Tuberous sclerosis can be suspected in utero. Heart tumors - the first sign of the disease - can be detected in the fetus from the 20th week of pregnancy. At birth, hypopigmented macules can be detected. These two features together make it possible to clinically diagnose tuberous sclerosis. However, genetic studies can reveal the deeper causes of the disease, as well as determine which gene caused the development of the disease. In addition to the correct and timely choice of therapy, these studies are also important for further family planning, in order to be sure that the birth of a child with tuberous sclerosis will not happen again in this family.”
Tuberous sclerosis is caused by mutations in the TSC1 and TSC2 genes. Fast and efficient molecular genetic diagnosis has become possible with the introduction of next generation sequencing (NGS) methods. The Laboratory of Epigenetics of the Research Centre for Medical Genetics has developed a unique protocol that makes it possible to make a diagnosis even in complex cases. For example, in cases of mosaicism: in case of ambiguous NGS results, an additional MLPA study is performed to identify large deletions. Re-delivery of the biomaterial is not required. The specialists of the Laboratory of Epigenetics studied the nature of the detected mutations and came to the conclusion that mosaicism is quite common. Mosaicism is a condition when the mutations that cause the disease were not inherited from the parents, but arose at an early stage in the development of the embryo. Such mutations are not present in all cells of the patient. This situation can lead to false negative diagnostic result because the proportion of cells with mutations in a blood sample may be very small. In such cases, exome and genomic sequencing may not be effective, and only very deep sequencing of two genes, TSC1 and TSC2, in combination with specially developed data analysis software, can reliably establish the molecular cause of the disease.
The tuberous sclerosis diagnostic program is ongoing and can be used by physicians throughout Russia. To do this, in accordance with the rules of the program, it is required to prepare a biomaterial and send it to the laboratory using a courier service.
Free program is available:
- for patients under 18 years of age
- for patients in whom the diagnosis of tuberous sclerosis is established clinically, but not confirmed genetically.
The drug for the treatment of children with tuberous sclerosis is purchased by the state fund for the support of children with severe and rare diseases "Krug dobra".
The tuberous sclerosis diagnostic program at the Research Centre for Medical Genetics is implemented with the support of Novartis Pharma LLC.