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Background: Currently more than 50 mutations of the INS gene are known to affect the various stages of insulin biosynthesis in the beta cells of the pancreas. However only individual cases of diabetes mellitus (DM) associated with heterozygous mutations in the coding region of the INS gene were reported in Russian Federation. We report a group of patients with a clinical manifestation of DM caused by mutations in both coding and non-coding regions of the INS gene. The patients with a mutation in the intron of the INS gene are reported for the first time in Russian FederationMaterials and methods: 60 patients with an isolated course of neonatal DM (NDM), 52 patients with a manifestation of DM at the age of 7–12 months and the absence of the main autoimmune markers of type 1 DM, 650 patients with the MODY phenotype were included in the study. NGS technology was used for molecular genetic research. Author’s panel of primers (Custom DNA Panel) was used for multiplex PCR and sequencing using Ion Ampliseq™ technology. The author’s panel “­Diabetes Mellitus” included 28 genes (13 candidate genes of MODY and other genes associated with DM).Results: 13 heterozygous mutations were identified in 16 probands and 9 relatives. The majority of mutations were detected in patients with PNDM (18.75%) and in patients with an onset of DM at the age of 7–12 months (9.6%). Mutations in the INS gene were detected in 2 patients (0.3%) in the group with the MODY phenotype. Mutations in the INS gene were not detected in patients with transient NDM (TNDM). Analysis of clinical data in patients with PND and onset of diabetes at the age of 7–12 months did not show significant differences in the course of the disease. The clinical characteristics of the cases of MODY10 and diabetes caused by a mutation in the intron of the INS gene are reported in details.Conclusion: The role of INS gene mutations in NDM, MODY, and DM with an onset at the age of 7–12 months was analyzed in a large group of patients. The clinical characteristics of DM due to a mutation in the intron of the INS gene are reported for the first time in the Russian Federation.

The liver experiences various changes with aging that could affect clinical characteristics and outcomes in patients with liver diseases. Both liver volume and blood flow decrease significantly with age. These changes and decreased cytochrome P450 activity can affect drug metabolism, increasing susceptibility to drug-induced liver injury. Immune responses against pathogens or neoplastic cells are lower in the elderly, although these individuals may be predisposed to autoimmunity through impairment of dendritic cell maturation and reduction of regulatory T cells. These changes in immune functions could alter the pathogenesis of viral hepatitis and autoimmune liver diseases, as well as the development of hepatocellular carcinoma. Collectively, aged patients show various changes of the liver and other organs that could affect the clinical characteristics and management of liver diseases in these patients.

The revealing of HFE gene mutations C282Y and H63D in 31 patients with chronic hepatitis and liver cirrhosis of different etiology was studied. Mutations were associated more often with male sex (52.9%) vs. female (21.4%) and alcohol abusing (46.2%) vs. non-drinkers (33.3%). In persons with mutations response to interferon therapy was poorer and fibrosis predominated over inflammation in liver bioptates.