Репозиторий Университета

© 2018, Dynasty Publishing House. All rights reserved. Chronic pancreatitis, being a complex multifactor clinico-genetic phenomenon, is a significant medical, social and economic problem. Study of pancreatitis remains a topical theme also for the paediatric cohort, especially taking into account practically similar morbidity rates in adults and children. The review presents information and analyzes main genetic risk factors of the development of pancreatitis. Mutations and polymorphisms of the CFTR, CTRC, SPINK1, CPA1, PRSS1, PRSS2 genes that are significant for functioning of the pancreas are discussed in detail. Examples of genetic variants associated with increased or decreased risks of developing disease are given. Special attention is paid to difficulties of interpreting the results of molecular-genetic testing associated with certain gene homology, presence of pseudogenes and disease cases conditioned by spontaneous mutation. Detection of genetic risk factors of chronic pancreatitis allows to early prevent the development of disease in the proband’s relatives, and also to take a more personalized approach to the patient’s treatment.

© 2018 Publishing House of the Union of Pediatricians. All rights reserved. Background. Cystic fibrosis is a hereditary disease that occurs as a result of mutations in the regulator gene of chloride ion transmembrane transport (CFTR). Finding mutations in the CFTR gene is necessary for identification of the clinical features of cystic fibrosis. Objective. Our aim was to identify genotype-phenotype correlations between mutations of the first class of pathogenicity and clinical manifestations of cystic fibrosis based on studying the prevalence and structure of CFTR gene mutations. Methods. The study included children under 18 years with cystic fibrosis admitted to hospital between 2013 and 2017. Biallelic mutations in the CFTR gene were the non-inclusion criterion. The CFTR gene variants were analyzed by next-generation sequencing method. Results. In 125 patients with cystic fibrosis, 59 different variants of the CFTR gene were detected, 11 of them not previously described. The most common was the deletion c.1521-1523del found in 98 (39.2%) of the 250 analyzed CFTR gene alleles and the deletion c.1545-1546del found in 22/250 (8.8%) alleles. It has been shown that the mutation c.1545-1546del, p.Y515∗ was more often found in children of the Chechen nation-odds ratio (OR) 139 (95% confidence interval 15-1,257). It has been established that meconium ileus, pancreatic deficiency and cirrhosis are more common in patients with mutations of the first category of pathogenicity: OR 3.9 (95% CI 1.0-15.0), 4.4 (95% CI 1.8-11.1), and 351 (95% CI 17.5-7,046), respectively. The association of CFTR gene mutations with the development of bronchiectases and polypous pancinusitis has not been found. Conclusion. Correlations between the genotype and clinical manifestations of cystic fibrosis in Russian children with CFTR gene mutations of the first class of pathogenicity have been established.