Спектр і частота мутацій гена ATP7B в різних популяціях та етнічних групах

Abstract

Wilson disease (WD) – autosomal recesive disorder for which effective inexpensive therapy has been developed. Such success was achieved through a detailed study of the structure of the protein, and the establishment of the correspondence between the individual Copper-binding ATPase domains, and the primary sequence of the gene encoding it. These studies gave an idea of the functioning and role of metal transport of each individual protein domain, and helped find ways to correct the pathology. Since copper is a part of almost all foods, and is coenzyme in many processes in the body, it is not possible to exclude this element from the diet. For people with a lack of excretion of copper ions from a cell inevitably there is a violation of the structure of the fatty acids of the cell membrane. Because of this, its integrity is lost, and as a result, degeneration of organs and tissues. Avoid such processes will help predictive testing, but the timely appointment of specific treatment. Diagnosis of this disease is complicated not only by non-specific manifestations, but by a wide range of mutations. Almost 300 mutations in ATP7B gene that are associated with WD development have been described. Although most WD-causing mutations are rare and only reported in single families, some are more common and account for a large portion of WD cases. Therefore, genetic testing of mutations will become possible only when the list of the most frequent for our population is formed, and an algorithm of medical genetic counseling of persons at high risk of development of the disease of Wilson-Konovalov is compiled. In Ukraine, such a study has not been conducted so there is no information about the frequency and range of mutations in this gene for our population. The majority of known mutations affecting this gene are frequent in different populations. It is important to diagnose Wilson disease as early as possible, since severe liver damage can occur before there are any signs of the disease. Thus, the purpose of my work is to conduct a study on the distribution of the frequency of mutations in the ATP7B gene on the basis of literature data in five neighboring countries: Poland, Austria, Latvia, Germany and Western Russia, in order to form the list of the most likely mutations in our population to improve WD diagnosis. The results obtained during the analysis of literary data showed that the most common cause of the disease among residents of Europe and western Russia is the mutation H1069Q. But the literature describes many other specific mutations to each individual population. Thus, it is expected that besides the major mutation of H1069Q, our population will have its own specific mutations. It is advisable to start a genetic study the mutation H1069Q and further sequencing of the exon 8 in person with WD.