Academic Journal
Genetic Heterogeneity of Inborn Errors of Immunity Revealed by Whole-Genome Sequencing: Insights from a Russian Patient Cohort.
| Τίτλος: | Genetic Heterogeneity of Inborn Errors of Immunity Revealed by Whole-Genome Sequencing: Insights from a Russian Patient Cohort. |
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| Συγγραφείς: | Petrusenko Y; Biotech Campus LLC., 117437 Moscow, Russia.; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia., Savin T; Saint Petersburg Pasteur Institute, 197101 St. Petersburg, Russia.; Department of Immunology, Pavlov First Saint Petersburg State Medical University, 197022 St. Petersburg, Russia., Sedykh A; Saint Petersburg Pasteur Institute, 197101 St. Petersburg, Russia., Chekanov N; Biotech Campus LLC., 117437 Moscow, Russia., Klimuk E; Biotech Campus LLC., 117437 Moscow, Russia., Ostankova Y; Saint Petersburg Pasteur Institute, 197101 St. Petersburg, Russia., Kuznetsova R; Saint Petersburg Pasteur Institute, 197101 St. Petersburg, Russia.; Department of Immunology, Pavlov First Saint Petersburg State Medical University, 197022 St. Petersburg, Russia., Chernyshova A; Saint Petersburg Pasteur Institute, 197101 St. Petersburg, Russia., Milichkina A; Saint Petersburg Pasteur Institute, 197101 St. Petersburg, Russia., Totolian A; Saint Petersburg Pasteur Institute, 197101 St. Petersburg, Russia.; Department of Immunology, Pavlov First Saint Petersburg State Medical University, 197022 St. Petersburg, Russia., Severinov K; Biotech Campus LLC., 117437 Moscow, Russia. |
| Πηγή: | International journal of molecular sciences [Int J Mol Sci] 2026 Sep 05; Vol. 27 (17). Date of Electronic Publication: 2026 Sep 05. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, [2000- |
| Ιατρικοί όροι (MeSH): | Whole Genome Sequencing*/methods , Agammaglobulinemia*/genetics , Genetic Heterogeneity*, Common Variable Immunodeficiency/genetics ; Agammaglobulinaemia Tyrosine Kinase/genetics ; Genetic Diseases, X-Linked/genetics ; Humans ; Male ; Female ; Russia ; Phenotype ; Cross-Sectional Studies ; Child, Preschool ; Child ; Cohort Studies ; Mutation |
| Περίληψη: | Identifying genetic cause(s) is a key step for management and treatment of patients with inborn errors of immunity (IEI). Here, in an observational cross-sectional genomic study, we analyzed whole-genome sequencing (WGS) data of 72 IEI patients from Saint Petersburg and Northwestern Russia: 42 patients with common variable immunodeficiency (CVID)-like phenotypes, 6 patients with clinically diagnosed X-linked agammaglobulinemia (XLA or Bruton's disease), and 24 patients with other forms of IEI. Causative pathogenic and likely pathogenic variants in BTK, CYBB, CHD7, AIRE, ATM, SBDS, NFKB1, and CTLA4 genes were identified in 14 (19%) patients. Variants of uncertain significance that could be linked to observed clinical phenotypes were detected in 6 patients. These included a BTK variant in a patient with Bruton's disease, variants in SH2D1A, SOCS1, and IKBKB in patients with CVID, and variants in CARD11 and CD40LG in patients with other forms of IEI. Additional rare variants that were mostly unique to individual patients were found in multiple IEI genes from the International Union of Immunological Societies (IUIS) Expert Committee 2024 list. In the CVID-like subcohort, pathway-level analysis of these rare variants revealed patterns associated with clinical manifestations. Taken together, our results expand the genetic characterization of an understudied regional IEI cohort, particularly of patients with CVID-like phenotypes, and identify genetic factors that are implicated in or may contribute to the disease. |
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| Contributed Indexing: | Keywords: DNA damage response; X-linked agammaglobulinemia (XLA); common variable immunodeficiency (CVID); immune dysregulation; immune signaling pathways; inborn errors of immunity (IEI); rare variants; whole-genome sequencing (WGS) |
| Substance Nomenclature: | EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase) |
| SCR Disease Name: | Bruton type agammaglobulinemia |
| Entry Date(s): | Date Created: 20260915 Date Completed: 20260915 Latest Revision: 20260916 |
| Update Code: | 20260916 |
| PubMed Central ID: | PMC13565858 |
| DOI: | 10.3390/ijms27177923 |
| PMID: | 42737820 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1422-0067 |
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| DOI: | 10.3390/ijms27177923 |