Problems and achievements in the study of clinical and genetic aspects of cystic fibrosis

Abstract

Cystic fibrosis is a common hereditary autosomal recessive disease characterized by pronounced genetic heterogeneity, associated clinical polymorphism, severe course and prognosis. The disease occurs worldwide in representatives of various populations and ethnic groups, with equal frequency among the male and female population. The molecular pathogenesis of the disease is based on disturbances in the synthesis, structure and function of the cystic fibrosis transmembrane conductance regulator protein (CFTR), which leads to various functional disorders in the work of chloride channels. As a result, the viscosity of secretions increases and exocrinopathy develops, which leads to disruption in the functioning of all organs and systems. The main cause of cystic fibrosis is a mutation in the CFTR gene. There are seven genetic classes of mutations in the CFTR gene, they mainly determine the severity of the disease. The main criterion in the diagnosis of cystic fibrosis is an increase in the concentration of chlorine ions in the secretion of sweat glands of more than 60 mmol/l when performing a sweat test using the classical Gibson–Cook method. An exception is a mutation in the CFTR– 3849+10kbC>T gene, which is associated with a normal or borderline sweat test result. For a long time, the treatment of patients suffering from cystic fibrosis was symptomatic, while the course of the disease remained severe and led to early mortality of patients. However, in recent decades, modern achievements in the field of studying the molecular genetic aspects of cystic fibrosis have made it possible to make a scientific breakthrough in the creation of pathogenetic therapy for this disease. New effective drugs that improve the health of patients and their quality of life have appeared. The relevance of studying the molecular mechanism of the disease for the development of a personalized approach in the treatment of cystic fibrosis is increasing, which is a promising direction on the way to gaining health for this category of patients.

Keywords

cystic fibrosis / history / genetics / clinical picture / neonatal screening / DNA diagnostics / cystic fibrosis transmembrane conductance regulator gene (CFTR) / targeted therapy

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