Numerous studies on the prevalence and associations of variants of the gene encoding the filaggrin protein with skin diseases have yielded conflicting and ambiguous results for different populations. For example, the R501X and 2282del4 variants are common among European patients with ichthyosis vulgaris (IV), but they have not been detected in Saudi Arabian patients with this disease. At the same time, the R501X variant is the most common among Mexican patients with IV. In addition, the R501X variant and the R501X and 2282del4 variants in the compound heterozygous state are associated with the severity of atopic dermatitis (AD) in Indian patients. Another common variant, R2447X, has been observed in Russian and Spanish patients with AD. It is worth noting that the 2282del4 variant is generally the most common in Russian patients with dermatoses. In a number of studies, these variants were not detected in patients with IV and AD from Asian countries. Some authors suggest that non-genetic factors may play an important role in the development of dermatoses.

Introduction. Preeclampsia is one of the most common obstetric problems, accounting for almost 15% of pregnancy-related pathologies. Various studies have evaluated the association of G1378T rs4961 variant in ADD1 gene with the risk of preeclampsia. However, results remain contradictory.

Aim. To examine the association of the ADD1 rs4961 genetic variant with the risk of preeclampsia through meta-analysis.

Methods. By searching according to the PRISMA protocol in the PubMed database, Google scholar search engine and the Russian scientific electronic library CyberLeninka.ru data on rs4961 variant of ADD1 gene in preeclampsia were collected from 8 studies. The ReviewManager (RevMan) 5.4 software was used to conduct meta-analysis. To assess the association of rs4961 variant of ADD1 gene with the risk of preeclampsia, odds ratio (OR) with a 95% confidence interval (CI) at allelic, dominant, and recessive models was calculated.

Results. No significant associations were found at any of these models: G versus T (OR = 1.55; 95% CI: 0.93, 2.58, P = 0.09), GG + GT versus TT (OR = 1.63; 95% CI: 0.96, 2.75, P = 0.07) and GG versus GT + TT (OR = 1.47; 95% CI: 0.92, 2.33, P = 0.10). Subgroup analysis revealed a statistically significant association between the ADD1 gene variant rs4961 and the risk of developing preeclampsia in Russian populations. The presence of the (TT) genotype doubles the risk of preeclampsia (OR = 2.07; 95 % CI: 1.00, 4.30, P = 0.05).

Conclusions. The results of the meta-analysis indicate no association between the ADD1 gene variant rs4961 and preeclampsia. However, subgroup analysis revealed that the (TT) genotype is associated with a high risk of preeclampsia in the Russian population. This suggests that the effect of the rs4961 variant on the pathogenesis of preeclampsia exhibits population specific characteristics. 

Introduction. Very-long-chain fatty acid acyl-CoA dehydrogenase deficiency (VLCADD) is a rare inherited disorder of fatty acid oxidation caused by mutations in the ACADVL gene. The prevalence of VLCADD is 1:30,000 – 1:100,000. The severe form of the disease presents in the neonatal period or within the first months of life and is characterized by cardiomyopathy, hydropericardium, arrhythmia, hypotension, hepatomegaly and hypoglycemia. Moderate VLCADD manifests in the first year of life or in early childhood, its symptoms include hepatomegaly and episodes of hypoketotic hypoglycemia. In mild cases, the first signs of the disease such as muscle pain, exercise intolerance, episodes of rhabdomyolysis appear in adolescence or later.

Purpose. To study the spectrum of mutations in the ACADVL gene in patients with VLCADD in the Republic of Belarus

Patients and methods. The study group included patients with VLCADD identified during selective screening for mitochondrial betaoxidation of fatty acids and other metabolic defects by tandem mass spectrometry (TMS), and their family members (4 probands, 2 parents, and a child of an adult patient). Genetic testing was performed via high-throughput sequencing combined with Sanger sequencing.

Results and discussion. Probands 1 and 2 suffered from acute metabolic decompensation, cardiomyopathy, hepatomegaly at the age of 3 months; the proband 2 also had progressive muscle hypotonia and severe hypoglycemia. Both children died at the age of 3.5 and 7 months, respectively. Probands 3 and 4 underwent TMS at 14 months and 25 years. In proband 3, the disease manifested with liver damage, episodes of hypoglycemia, cardiomyopathy. Symptoms of myopathy predominated in patient 4. Proband 1 was found to have a homozygous deletion p.Leu201TrpfsTer39 (NM_000018.4 (ACADVL): c.532delC) in exon 7 of the ACADVL gene. Proband 2 had missense mutation p.Gly253Val (NM_000018.4 (ACADVL): c.758G>T) in exon 9 and the frameshift mutation p.Pro296ArgfsTer17 (NM_000018.4 (ACADVL): c.887_888delCT) in exon 11. In Proband 3 we found p.Arg366Cys substitution (NM_000018.4 (ACADVL): c.1096C>T, rs771874163) in exon 11 and nonsense mutation p.Arg615Ter (NM_000018.4 (ACADVL): c.1843C>T, rs1057520507) in exon 20. Proband 4 had two likely pathogenic variants in intron 8 and exon 15: NM_000018.4 (ACADVL): c.752+2delC and p.Lys507Glu (NM_000018.4 (ACADVL): c.1519A>G, rs1217344032). The patient’s father and son were found to be carriers c.752+2delC mutation, and the mother had p.Lys507Glu in a heterozygous state.

Conclusion. VLCADD is a relatively rare hereditary metabolic defect in Belarus. The disease is characterized by pronounced clinical polymorphism, significant genetic heterogeneity, and the presence of evident genotype-phenotype correlations. As a result of the study, a spectrum of mutations in the ACADVL gene was established in patients with VLCADD in the Republic of Belarus, new pathogenic and likely pathogenic variants (p.Leu201TrpfsTer39, p.Gly253Val, p.Pro296ArgfsTer17 and c.752+2delC) were discovered. These variants were not registered in open databases and not previously described in available published works on VLCADD.

The article presents the results of a study on the structure of marriages in populations of Azerbaijan and the Pamirs. A comparative analysis of reproduction parameters in consanguineous and non-consanguineous marriages is provided. In the village of Abdal, Agdam district, Azerbaijan, 109 consanguineous marriages were identified (27.5% of the total number of marriages), with a genealogical inbreeding coefficient of F = 5.9%. Among the Rushan people of the village of Pastkhuf, Rushan district, Gorno-Badakhshan Autonomous Oblast, Tajikistan, located at an altitude of 2000 m above sea level, 16 out of 102 families were consanguineous. The inbreeding coefficient was

F = 5.9%. In Khuf (altitude 3000 m), 30 out of 101 families were consanguineous, with F = 5.4%. In Murghab, Murghab district, GornoBadakhshan Autonomous Oblast, Tajikistan (altitude 3800 m – 4200 m), 8 out of 179 Kyrgyz families were inbred, corresponding to an inbreeding value of F = 0.56%. In all studied populations, a similar trend was observed in families that had completed reproduction. In the post-reproductive age cohorts of women, the average number of births and the number of living children per woman were significantly higher in consanguineous marriages (p < 0.05) than in non-consanguineous marriages. In the population of Abdal, inbred families showed a pattern of increased birth rate, a higher average number of children, and a comparatively higher level of reproductive losses. The totality of the presented information allows us to conclude that the role of inbreeding in human populations is complex and ambiguous; the net effect on reproductive processes in a population depends on the simultaneous action of opposing tendencies and their interrelationship.

This paper describes a clinical case of a rare phenotype, Potter syndrome, resulting from the intrauterine development of end-stage renal failure. A rare, de novo missense variant in the WT1 gene WT1(NM_024426.6):c.1400G>A (p.Arg467Gln)  was detected and verified in the proband in a heterozygous state. This clinical case is the third patient with Potter syndrome associated with this genetic variant reported in the world literature and the first in the Russian Federation. Based on the available data, it is possible to suggest an earlier onset of nephrotic syndrome in patients with the mutation identified in the proband. 

Introduction. The diagnosis and treatment of cystic fibrosis (CF) is complicated by the possible presence of complex alleles. An allele is considered complex if it carries at least two genetic variants of the CFTR gene; in this case, each pathogenic variant can affect individual stages of CFTR protein biogenesis. The frequency and role of complex alleles are currently underestimated.

Objective. To describe a clinical case of cystic fibrosis in a patient carrying two complex alleles: c.[1521_1523delCTT;1399C>T];[c.1397 C>G;3209G>A], p.[Phe508del;Leu467Phe];[Ser466*;Arg1070Gln], the “traditional” name being [L467F;F508del]/[S466X;R1070Q]. 

Methods. We analyzed the patient’s medical history data, including outpatient records and hospital inpatient records from 2018 to 2023. We also analyzed CFTR gene sequencing data, ICM data from rectal biopsies, and data from forskolin-induced swelling of intestinal organoids obtained from rectal biopsies.

Results. The disease course in a 5-year-old child with the presence of two complex alleles [L467F;F508del]/[S466X;R1070Q] in the genotype is described. A severe course of the disease is demonstrated, early colonization with Pseudomonas aeruginosa, development of signs of chronic hypoxia, respiratory failure, course of polypous chronic rhinosinusitis, severe body weight deficit, poor compensation of intestinal syndrome. The results of functional tests performed using ICM data showed the absence of the CFTR chloride channel function, the forskolin-indused swelling on intestinal organoids revealed the absence of swelling when stimulated with forskolin and CFTR modulators. The combination of elexacaftor/tezacaftor/ivacaftor has an insignificant effect on the restoration of CFTR functional activity.

Conclusions. This is the first description of the clinical course of CF in a patient with two complex alleles, [L467F;F508del] and [S466X;R1070Q]. Using diagnostic methods such as the ICM and the forskolin-induced intestinal organelle swelling test, we demonstrated the absence of CFTR chloride channel function and a weak response to elexacaftor/tezacaftor/ivacaftor.

The results of a study on the gene pools of indigenous peoples of Southern Siberia – Altaians (Altai-kizhi, Telengits, Kumandins, Tubalars, Chelkans), Khakassians (Kachins, Koibals, Sagais) and Shors – based on uniparental (40 SNP and 17 STR markers of the Y-chromosome) and autosomal (7 SNPs in the genes ADH1B, ALDH2, CYP2E1, CYP1A1, PON1, GSTP1) DNA markers are discussed. The total sample size was 728 individuals. The Y-chromosome study revealed that the combined gene pool of the studied indigenous populations of Southern Siberia is represented by 21 haplogroups. A characteristic feature of the examined populations was the presence of both common (with a predominance of West Eurasian R1a and R1b and North Eurasian N1b, N1c1, Q) and unique haplogroups, reflecting the genetic history of gene pool formation. Based on data on polymorphic variants of selectively significant genes, the variability of MAF frequencies was shown. Cluster analysis based on data from two types of genetic markers, illustrated by multidimensional scaling methods, demonstrated a close, but not completely matching result.