Ring chromosome instability may influence a patient’s phenotype and challenge its interpretation. Here, we report a 4-year-old girl with a compound phenotype. Cytogenetic analysis revealed her karyotype to be 46,XX,r(22). aCGH identified a 180 kb 22q13.32 duplication, a de novo 2.024 Mb subtelomeric 22q13.32-q13.33 deletion, which is associated with Phelan-McDermid syndrome, and a maternal single gene 382-kb TUSC7 deletion of uncertain clinical significance located in the region of the 3q13.31 deletion syndrome. All chromosomal aberrations were confirmed by real-time PCR in lymphocytes and detected in skin fibroblasts. The deletions were also found in the buccal epithelium. According to FISH analysis, 8% and 24% of the patient’s lymphocytes and skin fibroblasts, respectively, had monosomy 22. We believe that a combination of 22q13.32-q13.33 deletion and monosomy 22 in a portion of cells can better define the clinical phenotype of the patient. Importantly, the in vivo presence of monosomic cells indicates ring chromosome instability, which may favor karyotype correction that is significant for the development of chromosomal therapy protocols.

The study aimed to evaluate the changes of hippocampal neurogenesis in a new model of global transient cerebral ischemia which was performed by the occlusion of the three main vessels (tr. brachiocephalicus, a. subclavia sinistra, and a. carotis communis sinistra) branching from the aortic arch and supplying the brain. Global transitory cerebral ischemia was modeled on male rats (weight = 250–300 g) under chloral hydrate with artificial lung ventilation. Animals after the same surgical operation without vessel occlusion served as sham-operated controls. The number of DCX-positive (doublecortin, the marker of immature neurons) cells in dentate gyrus (DG) and CA1-CA3 fields of hippocampus was counted at the 31^st day after ischemia modeling. It was revealed that global cerebral ischemia decreased neurogenesis in dentate gyrus in comparison with the sham-operated group (P<0.05) while neurogenesis in CA1-CA3 fields was increased as compared to the control (P<0.05).

Our understanding of human genes - particularly their structure, functions, and regulatory mechanisms - is still limited. The biological role of approximately 20 % of human proteins has not been established yet, and the molecular functions of the known part of the proteome remain poorly understood. This hinders progress in basic and applied biological and medical sciences, especially in treating hereditary diseases, which are caused by mutations and polymorphic variants in individual genes. Therefore, it is crucial to comprehend the mechanisms of protein functioning to address this problem. This further emphasizes the importance of investigating gene functions and molecular pathogenetic pathways associated with single-gene inherited diseases. This review focuses on the TCF4 gene that encodes a transcription factor crucial for nervous system development and functioning. Pathogenic variants in this gene have been linked to a rare genetic disorder, Pitt–Hopkins syndrome, and TCF4 polymorphic variants are associated with several socially significant diseases, including various psychiatric disorders. The pathogenetic mechanisms of these conditions remain unexplored, and the knowledge about TCF4 upregulation and its target genes is limited. TCF4 can be expressed in various isoforms due to the complex structure and regulation of its gene, which complicates the investigation of the protein’s functions. Here, we consider the structure and functions of the TCF4 transcription factor. We discuss its potential target genes and the possible loss-of-function pathogenetic mechanisms identified in animal and cellular models of Pitt–Hopkins syndrome. The review also examines the advantages and limitations of potential therapies for Pitt–Hopkins syndrome that are based on TCF4 dosage compensation or altering the activity of TCF4 target genes.

The effect of knockout and overexpression of the ADAMTS1 on the radiation-induced response in HeLa cell line was analyzed. The cell line with the ADAMTS1 gene knockout was created using the CRISPR/Cas9 genome editing technology. The ADAMTS1 gene overexpression was ensured by transient transfection of the plasmid containing the gene of interest. Clonogenic survival, micronuclei frequency, and the γH2AX and 53BP1 foci level after irradiation with 2–8 Gy of γ rays were assessed. It was shown that the HeLa cell line with the ADAMTS1 gene knockout was characterized by a 1.9-fold decrease in clonogenic survival after an irradiation dose of 2 Gy (p < 0.05) and an increase in micronuclei frequency (55.3 ± 8.3‰) in comparison with intact HeLa (36.0 ± 7.2‰, p < 0.05), but did not differ in the DNA repair foci level. Transfection of the plasmid carrying the ADAMTS1 gene into HeLa cell line with the ADAMTS1 gene knockout led to a decrease in the radiation-induced micronuclei frequency from 55.3 ± 8.3 to 28.7 ± 10.3‰ (p < 0.05), which was comparable with the micronuclei frequency in the original HeLa cell line after irradiation (36.0 ± 7.2‰). Our results indicate that the ADAMTS1 gene is involved in radiation-induced cellular response in the HeLa cell line.

Проведен анализ влияния дифференциальной экспрессии гена ADAMTS1 на радиационно-индуцированный ответ в клеточных линиях HeLa с нокаутом и сверхэкспрессией гена ADAMTS1. Клеточная линия с нокаутом гена была получена с помощью системы редактирования генома CRISPR/Cas9. Сверхэкспрессия гена ADAMTS1 обеспечивалась с помощью временной трансфекции плазмиды, содержащей кодирующую последовательность изучаемого гена. После воздействия на клеточные линии γ-излучением в диапазоне доз 2–8 Гр оценена клональная выживаемость, уровень микроядер и фокусов белков репарации ДНК γH2AX и 53BP1. Показано, что клеточная линия HeLa с нокаутом гена ADAMTS1 характеризуется снижением клональной выживаемости в 1.9 раз (p < 0.05) после облучения в дозе 2 Гр и повышенной частотой микроядер (55.3 ± 8.3‰) по сравнению с исходной клеточной линией HeLa (36.0 ± 4.2‰, p < 0.05), но не отличается по уровню фокусов белков репарации ДНК. Трансфекция клеточной линии HeLa с нокаутом ADAMTS1 плазмидой, несущей кодирующую последовательность изучаемого гена, приводит к снижению частоты радиационно-индуцированных микроядер с 55.3 ± 8.3 до 28.7 ± 10.3‰ (p < 0.05), что сопоставимо с частотой микроядер в исходной клеточной линии HeLa после облучения (36.0 ± 7.2‰). Полученные данные свидетельствуют об участии ADAMTS1 в формировании радиационно-индуцированного ответа в данном типе клеток.