The main clinical characteristics of a large group of 30 lysosomal storage diseases (LSD), including mucopolysaccharidoses (MPS), sphingolipidoses (SLD), and glycoproteinoses (ILD), are summarized. The purpose of the work is to identify general and particular patterns in the manifestation of LSD. For all LSD, a syndromic nature of the lesion is observed. Almost half of the studied diseases are characterized by a hurler-like phenotype (GPF). The most common clinical manifestations of LSD are neurological anomalies, ophthalmopathies, hearing impairment, hepato- and splenomegaly, hernias, skeletal dysplasia, stiffness and joint contractures. Patients die most often from cardiovascular insufficiency and recurrent infections. Hematological, cutaneous, and nephrological manifestations are observed only in some LSD. For many LSD (63%), clinical polymorphism is typical both in the onset and in the existence of allelic disease series. In almost a third of cases (27%), genetic heterogeneity is noted, so, a similar nature of the course of diseases caused by mutations in different genes. LSD - are rare diseases with frequencies ranging from 1:40,000 to 1:500,000 newborns. Some more rare LSD have also been described. In this case, the total frequency of LSD is 1: 7-8 thousand newborns. Some LSD are predominantly distributed in certain ethnic groups, the classic example of which are Jews of Eastern European origin.

Lysosomal storage diseases (LSDs) comprise the group of about 70 disorders characterized by lysosomal dysfunction, most of which have autosomal recessive trait of inheritance. Despite the fact that each nosology itself is a rather rare disease, the overall prevalence of LSD ranges from 1:5,000 to 1:7,500 among newborns, with a higher incidence among the population (Finns, Ashkenazi Jews). The accumulation of macromolecules in the organelles of endosomal-autophagic-lysosomal system is considered to be a common link of the pathogenesis for all LSD. Last decade, there has been a particular interest in the common ground of pathogenesis underlying the development of lysosomal diseases and frequent neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis. This review we provide the main molecular mechanisms underlying these two human disease groups. Understanding the resemblance of the pathogenesis of theses groups can help for look at their etiology from the other side and open new perspectives on the drug therapy.

The expanding horizons of interdisciplinary research made it possible to take a fresh look at the possibilities of solving a number of problems of historical and genetic research, namely, the ratio of ethnicity and population, and effective analysis of the gene pool of an ethnic group. In the present work, the following tasks have been set and consistently solved: a) elucidation of the degree of genetic differentiation of sub-ethnic groups of Kalmyks; b) determination of the ethnogenetic ties of the Kalmyks with the Oirat groups of Western Mongolia; c) clarification of controversial issues of ethnogenesis of groups of Sart-Kalmaks of Kyrgyzstan; d) determination of the haplogroup of the Y-chromosome in the descendants of the Khoshut clan of Kalmykia, leading their ancestry from Khabutu Khasar. The material for the study of the gene pool was the samples of venous blood from 373 people (men) collected in subpopulations of Kalmyks of the Russian Federation: Torguts (58), Derbets (70), Buzava (52), Khoshuts (28); Western Mongolia: Torguts (47), Derbets (41), Khoshuts (18) and Sart-Kalmaks of Kyrgyzstan (61). Microsatellite analysis was performed in 78 samples using 23 short tandem STR repeats. According to the analysis of the Y-chromosome, it was shown that the sub-ethnic groups of Kalmyks are poorly differentiated, which indicates the unity of the Kalmyk population. It was revealed that the subethnic groups of Derbets and Torguts of Western Mongolia, despite significant isolation by distance for 400 years, have an identical picture of the distribution of Y-chromosome haplogroups. For the first time it was discovered that the descendants of the Khoshut clan, tracing their ancestry from the younger brother of Genghis Khan, are carriers of the Y-chromosome haplogroup C3c1b-F6379. For the populations of the Oirats of Mongolia and the Kalmyks of Russia, it is major and occupies more than 50% of the sample. Strict patrilineal exogamy which regulates marriages between clan members related by father and the patrilineal nature of genealogical kinship, leading to endogamous tribes, contributed to the wide distribution of this haplogroup in Kalmyks and Oirats.

In this work, for the first time, an in silico evaluation of the possible pathogenic effect of the c.441G>A p.(Met147Ile) variant of uncertain significance of the SLC26A4 gene on the function/structure of the pendrin (SLC26A4) protein was performed using the AlphaFold neural network algorithm, which predicts the spatial structure of the protein when such a structure is unknown. Based on the predicted model of the human pendrin tertiary structure, the alignment of the mutant (p.Met147Ile) and native protein structures was carried out using the PyMOL graphics program. As a result, the calculated similarity index of the two structures RMSD (root-mean-square deviation of atomic positions) was less than 2 Å, which indicates that the missense p.(Met147Ile) substitution theoretically does not violate the structural stability of the protein. Probably, the pathogenic effect of the mutation occurs at the functional level, since the analyzed p.(Met147Ile) is located in a critical region of the core domain (an evolutionarily conserved α3-helix region of the TMD), the disruption of which can lead to incorrect substrate transport or the appearance of toxic conformations in the transmembrane region.

Genetic variations that influence DNA repair efficiency potentially may contribute to atherosclerosis-indused diseases susceptibility. We identified eligible studies through a comprehensive literature search to determine whether an association exists between XRCC1 gene polymorphism with such atherosclerosis-indused diseases as coronary artery disease (CAD) and infarct. Findings were assessed using the odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed- or random-effects model, based on the heterogeneity of the studies. 6 eligible studies were finally included in this meta-analysis. Our pooled analysis found that XRCC1 polymorphisms were significantly associated with atherosclerosis-indused diseases susceptibility in homozygote comparisons (Arg194Trp in a total population: OR = 1.42, 95% CI = 1.07-1.89; Arg399Gln in a Caucasian population: OR = 1.68, 95% CI = 1.07-2.63; Arg399Gln in a total population: OR = 1.46, 95% CI = 1.10-1.92) and under dominant genetic model (Arg194Trp in a total population: OR = 0.66, 95% CI = 0.5-0.86; Arg399Gln in a Caucasian population: OR = 0.65, 95% CI = 0.43-1.00; Arg399Gln in a total population: OR = 0.71, 95% CI = 0.54-0.93). Based on our meta-analysis, we concluded that the XRCC1 gene polymorphisms, Arg194Trp and Arg399Gln, may be associated with CAD and stroke susceptibility. However, additional, comprehensive and well-designed studies are warranted to confirm these findings.