Hereditary breast cancer appears in 5-10% all breast cancers and manifests in founder mutations (mutations, which charachterised particular region). The article goal: to detail information about populatiom polymorphisms (ethnic polymorphisms) genes predisposition to hereditary breast cancer: BRCA1/2, CHEK2 and PALB2 for applying the markers of these genes in medical practice. These genes contain the highest quantity of pathogenic mutations correspondingly the data base oncoBRCA.com. Searching the literature was conducted in web base data: MEDLINE, Scopus, Web of Science, ClinVar, Cancer Tomorrow and Global cancer observatory. In the world population of patients with breast cancer are quantity and quality differencies of polymorphisms in genes BRCA1 and BRCA2. It has developed the standart the PCR-panel from eight mutations in BRCA1/2 genes which can found in patients with clinical features of hereditary breast cancer in Russia (slavic population) (5382insC, 4153delA, 185delAG, 3819delGTAAA, 3875delGTCT, 300T>G, 2080delA BRCA1; gene 6174delT BRCA2 gene)). Also frequency and quality of the polymorphiysms in the world populations can be different in CHEK2 and PALB2 genes. The review can be useful for medical geneticist and molecular biologists in applying the information about possibility the testing of the mutaions some genes for effective diagnostics of the hereditary breast cancer when patients can be different content (different populations).

This article presents the clinical and genetic characteristics of 15 cases of urea cycle disorders (UCD) identified in Russia in 2023 during the expanded neonatal screening. Following the primary screening conducted in regional centers, a group of newborns was formed for the confirmatory diagnostics at the Research Centre for Medical Genetics (N=203). The concentrations of amino acids and acylcarnitines in the blood were remeasured using MS/MS, and urinary organic acid concentrations were measured using GC-MS. Molecular genetic analysis of the coding regions of the ASS1, ASL, and ARG1 genes was performed. Citrullinemia type 1 was genetically confirmed in 9 patients, while argininosuccinic aciduria was confirmed in 6 patients. The frequency of UCD was 1:82,093 live newborns. Five newborns diagnosed with citrullinemia type 1 had biallelic mutations in the ASS1 gene, and four patients had mutations in a homozygous state. Three newborns diagnosed with argininosuccinic aciduria had biallelic mutations in the ASL gene, while the other three patients had mutations in a homozygous state. Previously undescribed variants in a heterozygous state were identified: c.682A>G (p.Asn228Asp) in the ASL gene, as well as c.420+3A>G and c.175-2A>G in the ASS1 gene. At the time of examination, symptoms were observed in 13 newborns (87%). The mortality rate during the first months of life (from 5 to 67 days) was high (47%). Blood citrulline concentrations were elevated in all patients both during the primary screening and the retest. Blood citrulline concentrations in patients with citrullinemia type 1 with lethal outcome was statistically significantly higher compared to live newborns with the same diagnosis (p=0.018). In all cases of citrullinemia type 1 with lethal outcome, citrulline concentration was >1000 μmol/L. Thus, blood citrulline concentration can serve as a marker for the severity of citrullinemia type 1.

Background. Approximately 20% of induced pluripotent stem cell (iPSC) lines spontaneously acquire chromosomal abnormalities, which hinders their use in research and medical applications. One rational approach for routine monitoring of genetic stability in iPSCs is the targeted detection of recurrent karyotype anomalies, 20-60% of which may involve trisomy of chromosome 12. Trisomy 12 leads to impaired differentiation capacity and replication dynamics and is associated with the rapid displacement of the euploid clone.

Aim. To develop a protocol for the production of fluorescent DNA probes for the detection of chromosome 12 aneuploidy.

Results. A two-stage protocol for obtaining DNA probes based on PCR, using genomic DNA as the template, has been developed, followed by direct click-labeling with a fluorochrome. Hybridization conditions have been optimized for iPSC lines with known euploid and aneuploid karyotypes, confirming the effectiveness and specificity of detecting chromosome 12 on metaphase spreads and in     interphase nuclei.

Conclusions. FISH using custom DNA probes enhances the availability of chromosome 12 copy number analysis in laboratories, facilitating the timely detection of functionally significant genetic abnormalities in cell lines.

Despite a significant number of studies devoted to the transcription factor E2F1, its functional role in cellular processes remains ambiguous. Depending on the context, E2F1 can either support cell survival or initiate apoptosis. The present work is devoted to the possibility of using E2F1 as a therapeutic target for the combined treatment of malignant neoplasms, including through the use of inhibitors. However, the available data also indicate a potentially opposite effect of E2F1, which can negatively affect the effectiveness of therapy. This emphasizes the relevance of an in-depth study of the functional activity of E2F1 in various conditions. Transcription factors of the E2F family, including E2F1, demonstrate both overlapping functions and unique properties inherent in its individual members. Suppression of the expression of individual representatives of the family makes it possible to more accurately assess their contribution to key cellular processes. As part of the study, a subline of A549 lung cancer cells with a knockout of the E2F1 gene, carried out using CRISPR/Cas technology, was developed. Based on this cell model, experiments are planned to be carried out aimed at studying the role of E2F1 in various conditions, including responses to chemotherapeutic effects

Background. Preeclampsia (PE) is a serious complication related to high blood pressure during pregnancy, affecting approximately 2-15% of pregnant women. This condition is marked by elevated blood pressure and poses substantial risks to both maternal and fetal health. Identifying early biomarkers for PE is a key focus in the effort to prevent this potentially dangerous condition in a timely manner.

Aim: The aim of this study was to identify potential in silico biomarkers for hypertensive complications during pregnancy by analyzing findings from both international and domestic genome-wide association studies (GWAS).

Methods. The research involved the examination of summary statistics from international GWAS focused on hypertensive complications of pregnancy, which were then cross-validated against data from the Biobank Russia (BBRU) project.

Results. The analysis revealed 44 single nucleotide polymorphisms (SNPs) linked to preeclampsia (PE) and/or other hypertensive complications during pregnancy across both discovery and validating GWAS. Notably, the rs10843404 SNP variant in the PZP gene was statistically significant (p < 0.05) in the domestic GWAS. Additionally, four other SNPs located in the FLT1 and FGF5 genes showed a tendency toward statistical significance (p < 0.1).

Conclusions. The findings from the replication analysis, along with literature data, indicate that the product of the PZP plays a crucial role in the development of hypertensive forms of PE. The limited number of replicated loci in the Russian cohort may reflect genetic differences in PE across populations, highlighting the need for further studies involving larger sample sizes to enhance statistical power and provide a more comprehensive understanding of genetic risk factors for PE in the Russian population.

Introduction. Since 01/01/2023, expanded neonatal screening (ENS) has been carried out in the Russian Federation, where blood is collected from newborns in the first 24-48 hours of life; to diagnose phenylketonuria, instead of the previously used fluorimetric method, the tandem mass spectrometry (TMS) method has been used.

Purpose. To evaluate the results of screening newborns for PKU in relation to earlier blood sampling and a different method of determining blood phenylalanine (Phe).

Methods. An analysis of the results of examinations for PKU of children born in the Krasnodar region from 1 January 2023 to 31 July 2024 was carried out. Capillary blood sampling was carried out in the first 24-48 hours of life in full-term newborns and on the 7th day in premature infants. The concentration of Phe, tyrosine (Tyr) in the blood and the Phe/Tyr ratio were determined by TMS on a QSight 225MD Screening System (Finland) using NeoBase 2 kits.

Results. During this period, 81,383 children were born in the region, 81,193 (99.8%) were examined within the framework of the ENS. 32 children with hyperphenylalaninemia (HPA) and 3 heterozygous carriers of pathogenic variants in the PAH gene were identified, the frequency of the disease was 1:2537, which is 2.9 times higher than the frequency of PKU previously determined according to neonatal screening (NS). The threshold level of Phe was determined to be 20-97 μM/l, the Phe/Tyr ratio was 0-2.2. Of the 32 children with hyperphenylalaninemia (HPA), 13 were diagnosed with classic PKU, and 19 were diagnosed with mild HPA. During examination in maternity hospitals, the blood Phe level in identified patients ranged from 96 to 602 μM/l, the Phe/Tyr ratio – from 0.9 to 14.0. According to the results of the molecular genetic study, 2 children (6.3%) were identified with 2 mild mutations in the PAH gene, 16 (50%) with 1 mild and 1 severe mutation, 7 (21.9%) with two severe mutations, 7 (21.9%) – with 1 or 2 mutations of uncertain severity.

Conclusions. Examination of newborns for PKU as part of the ENS allows for the timely identification of children not only with classic PKU, but also with mild forms of HPA. Changing the timing of newborn screening during ENS requires careful consideration of threshold  levels of Phe and the Phe/Tyr ratio to prevent missing children with HPA.

In most women, pathogenic variants on the X chromosome are not expressed or are expressed in a weakened form, since they are heterozygotes for the pathogenic variant and one of the X chromosomes in women is always inactivated. However, 15–20% of genes on the human X chromosome escape from inactivation and are expressed from both chromosomes. In an 11-year-old patient with encephalopathy of combined genesis and delayed speech development, a duplication on the long arm of the X chromosome was detected by standard cytogenetic analysis. Using chromosomal microarray analysis, we clarified the localization of the rearrangement: arr[GRCh38] Xq22.3q25(104563898_122794771)x3. The duplication have size of 18 Mb. The patient had extremely asymmetric inactivation of the X chromosome (95%). Nine genes that escape from inactivation are localized in the duplication region. An excessive dose of the ALG13 gene, pathogenic variants of which are associated with developmental encephalopathy and epileptic encephalopathy 36, may be the cause of the development of clinical symptoms in the patient.