{ "abstract": "Background\n\nSerine-threonine kinase 4 (STK4) deficiency is a rare primary immunodeficiency disorder characterized by progressive T-cell lymphopenia, recurrent infections, cutaneous warts, abscesses, autoimmunity, and cardiac manifestations. This condition is associated with impaired immune surveillance, predisposing patients to severe infections and immune dysregulation.Case presentation\n\nHerein, we report a consanguineous Persian family with two affected siblings presenting with clinical features consistent with STK4 deficiency. At presentation, patient 1, a 30-year-old male, exhibited markedly reduced CD4 + lymphocyte counts. He presented with chronic diarrhea, fever, and oral thrush during infancy, followed by recurrent episodes of pneumonia that required hospitalization since the age of 4 months. At 18 years of age, he developed progressively worsening localized warts on both hands and feet. He also experienced a prolonged episode of bacterial meningitis lasting one month. Despite these infections, his serum immunoglobulin levels remained within the normal range. Patient 2, his affected 20-year-old sister, similarly presented with reduced CD4 + lymphocyte counts. She had multiple hospitalizations during her first year of life due to pneumonia and chronic diarrhea. By the age of 11, she developed localized warts on her hands and feet. In contrast, their parents and four other siblings remained asymptomatic, with no history of recurrent infections or cutaneous warts.Conclusion\n\nNext-generation sequencing (NGS)-based targeted sequencing and Sanger segregation analysis revealed a homozygous frameshift mutation in the STK4 gene (p.Leu275AlafsTer21) in both affected siblings. The parents were heterozygous carriers of the mutation, while the other siblings were either heterozygous or wild type. Functional studies would be needed to further elucidate the pathogenic mechanism of this mutation. Long-term follow-up of these patients is essential to monitor for any additional manifestations associated with STK4 deficiency and to provide timely interventions.", "abstract_shown": true, "affiliations": [ "School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.", "Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.", "Research Center for Immunodeficiencies (RCID), Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran, Dr. Qarib St, Keshavarz Blvd, 14194.", "Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.", "St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.", "Division of Pediatrics, Boston Children's Hospital, Boston, MA, USA.", "International Hematology/Oncology of Pediatrics Experts (IHOPE), Universal Scientific Education and Research Network (USERN), Boston, MA, United States.", "Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.", "CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.", "Clinic for Pediatric Immunology and Rheumatology, Center for Pediatrics and Adolescent Medicine, University Hospital Bonn, Bonn, Germany.", "Research Center for Immunodeficiencies (RCID), Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran, Dr. Qarib St, Keshavarz Blvd, 14194. rezaei_nima@tums.ac.ir.", "Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. rezaei_nima@tums.ac.ir.", "Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. rezaei_nima@tums.ac.ir." ], "article_type": "review", "arxiv": null, "author_total": 10, "authors": [ { "affs": [ 0 ], "name": "Hanye Sohrabi" }, { "affs": [ 0 ], "name": "Mohammad Ghavam" }, { "affs": [ 1 ], "name": "Hossein Esmaeilzadeh" }, { "affs": [ 0, 2, 3 ], "name": "Niloufar Yazdanpanah" }, { "affs": [ 2, 4 ], "name": "Samaneh Zoghi" }, { "affs": [ 5, 6 ], "name": "Elham Rayzan" }, { "affs": [ 4, 7, 8 ], "name": "Raul Jimenez-Heredia" }, { "affs": [ 4 ], "name": "Anna Segarra-Roca" }, { "affs": [ 4, 7, 8, 9 ], "name": "Kaan Boztug" }, { "affs": [ 10, 11, 12 ], "name": "Nima Rezaei", "orcid": "0000-0002-3836-1827" } ], "bibtex": "https://research.draconitic.com/paper/dj671fktbtejs.bib", "cited_by": 0, "doi": "10.1186/s13256-026-06435-8", "fulltext_url": "https://europepmc.org/articles/PMC13721605", "id": "dj671fktbtejs", "issns": [ "1752-1947" ], "landing_url": "https://europepmc.org/article/MED/42958346", "language": "eng", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Case Report" ], [ "openalex", "2403|Immunodeficiency and Autoimmune Disorders" ] ], "openalex": "W7172339918", "pdf_url": "https://europepmc.org/articles/PMC13721605?pdf=render", "pmcid": "PMC13721605", "pmid": "42958346", "published": "2026-08-03", "publisher": "BMC", "ris": "https://research.draconitic.com/paper/dj671fktbtejs.ris", "sources": [ { "first_seen": "2026-11-01T00:20:47Z", "native_id": "MED:42958346", "source": "europepmc", "url": "https://europepmc.org/article/MED/42958346" }, { "first_seen": "2026-11-03T12:22:16Z", "native_id": "PMC13721605", "source": "pmc", "url": "https://doi.org/10.1186/s13256-026-06435-8" } ], "subjects": [ { "field": "biology", "origin": "openalex:2403|Immunodeficiency and Autoimmune Disorders", "subfield": "immunology" } ], "title": "A novel STK4 mutation in two siblings with CD4 lymphopenia, recurrent infections and warts: a case report and review of the literature.", "title_text": "A novel STK4 mutation in two siblings with CD4 lymphopenia, recurrent infections and warts: a case report and review of the literature.", "type": "peer-reviewed", "updated_at": "2026-11-03T12:22:16Z", "url": "https://research.draconitic.com/paper/dj671fktbtejs", "venue": "Journal of medical case reports", "versions": [] }