Genome instability in induced pluripotent stem cells (IPSC) poses a significant challenge for their use in research and medicine. Cataloging and precisely describing all the identified aberrations that arise during cell reprogramming, expansion, and differentiation is essential for improving approaches to instability prevention and ensuring genetic quality control. We report the karyotypic analysis of 65 cell lines derived from skin fibroblasts, urinal sediment, and peripheral blood mononuclear cells of 33 individuals, 82% of whom suffer from monogenic genetic disorders not associated with genetic instability. Trisomy of chromosomes 20 and 8 was revealed recurrently, while the 1q arm was the most frequently affected region involved in interstitial duplications and unbalanced translocations with chromosomes 15 and 18. The localization of rearrangement breakpoints identified by SNP arrays within the large DCC gene and histone gene clusters links genetic instability in IPSCs to replication-stress-induced chromosome breakage at common and early replicating fragile sites.

This paper is a systematic review of the published data describing genetic risk factors for pulmonary diseases caused by nontuberculous mycobacteria (nontuberculous mycobacterial pulmonary disease - NTM-PD). The aim of the study is to compile a specific list of genetic markers associated with the risk of developing NTM-PD. This literature review was prepared according to PRISMA criteria and was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (registration number CRD42019128569). In the process of work, a great number of articles from PubMed, Google Scholar, and ScienceDirect databases have been studied. Using careful analysis and selection procedures, a list of 14 genetic variants associated with an increased risk of developing NTM-PD was generated. SLC11A1, NLRP3, TLR2, CFTR, IFNGR1, PDCD1 genes have been found to refer to these variants as well as variants in the intergenic regions affecting expression of STK17A, IFNL3, TNF, IL10 genes. The products of these genes take different roles in regulating the response to various pathogenic factors, and some of them are poorly understood. For a more precise and detailed explanation of the influence of these genetic variants, further studies in patient groups of different populations with the evaluation of different combinations of variants and intergenic interaction are required.

The article presents a systematic review of publications devoted to the study of genetic markers of severe pneumonia.The aim of the study was to compile a list of genetic markers that contribute to a severe course of pneumonia on the basis of the published data.In the current study, we searched for and analyzed articles published between January 2000 and April 2021. Following the search for and subsequent selection of articles, a list of 10 publications was compiled, which demonstrated a clear association of certain gene variants with severe and complicated pneumonia. Finally, we made a list of genetic markers of severe pneumonia consisting of 16 polymorphisms in 12 genes (CD86, IL6, IL10, PAI1, TNFα, HMGB1, ATG16L1, AGTR1, GCLC, CAT, IFNγ, FCGR2A).These genetic markers of severe and complicated pneumonia are responsible for various innate immune responses. The odds ratio for complicated pneumonia with a risk allele in the polymorphisms in the mentioned genes ranges from 1.39 to 4.28. To understand molecular and genetic mechanisms of severe pneumonia, further investigation of the effect of these genetic factors on the outcomes of pneumonia in different groups of patients with a simultaneous assessment of the cumulative effect of genetic variants and genetic interactions is required.

Background: ARCN1-related syndrome (short stature-micrognathia syndrome, SSMG; OMIM #617164) is an autosomal dominant disorder caused by loss-of-function variants in the ARCN1 gene, which encodes the δ-COP (COPD) subunit of the COPI coatomer complex. The condition is classically characterized by intrauterine growth restriction (IUGR), short stature with rhizomelic shortening, microcephaly, micrognathia, facial dysmorphism, and global developmental delay. Methods: Clinical examination, blood tests and genetic analysis were performed. Whole-exome sequencing and Sanger analysis were conducted, followed by bioinformatics analysis and ACMG-based variant interpretation to identify and characterize the pathogenic variant. Results: We report a male proband with a previously undescribed variant in the ARCN1 gene, presenting with an atypical phenotype. Notably, the patient lacked the classical syndromic features, including short stature, microcephaly, IUGR, and developmental delay. The predominant clinical manifestation was transient hepatic dysfunction occurring during febrile episodes, which resolved between acute events. On physical examination, rhizomelic shortening and dysmorphic facial features, including mild micrognathia, were found. Overall, identified symptoms were mild in severity, which may be associated with the variant’s location within the gene. Conclusions: We describe a novel likely pathogenic variant in the ARCN1 gene associated with a mild phenotype of SSMG. This case expands the phenotypic spectrum of ARCN1-related syndrome and highlights the importance of considering this diagnosis in patients with unexplained recurrent liver injury, even in the absence of classical syndromic features.