A novel STK4 mutation in two siblings with CD4 lymphopenia, recurrent infections and warts: a case report and review of the literature.
13 affiliations
- 1School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
- 2Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
- 3Research Center for Immunodeficiencies (RCID), Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran, Dr. Qarib St, Keshavarz Blvd, 14194.
- 4Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
- 5St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.
- 6Division of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
- 7International Hematology/Oncology of Pediatrics Experts (IHOPE), Universal Scientific Education and Research Network (USERN), Boston, MA, United States.
- 8Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
- 9CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
- 10Clinic for Pediatric Immunology and Rheumatology, Center for Pediatrics and Adolescent Medicine, University Hospital Bonn, Bonn, Germany.
- 11Research Center for Immunodeficiencies (RCID), Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran, Dr. Qarib St, Keshavarz Blvd, 14194. [email protected].
- 12Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. [email protected].
- 13Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. [email protected].
Abstract
Background
Serine-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
Herein, 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
Next-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.
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BibTeX
@article{sohrabi2026novel,
title = {{A novel STK4 mutation in two siblings with CD4 lymphopenia, recurrent infections and warts: a case report and review of the literature.}},
author = {Hanye Sohrabi and Mohammad Ghavam and Hossein Esmaeilzadeh and Niloufar Yazdanpanah and Samaneh Zoghi and Elham Rayzan and Raul Jimenez-Heredia and Anna Segarra-Roca and Kaan Boztug and Nima Rezaei},
journal = {Journal of medical case reports},
year = {2026},
month = aug,
doi = {10.1186/s13256-026-06435-8},
url = {https://europepmc.org/article/MED/42958346},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A novel STK4 mutation in two siblings with CD4 lymphopenia, recurrent infections and warts: a case report and review of the literature.
AU - Hanye Sohrabi
AU - Mohammad Ghavam
AU - Hossein Esmaeilzadeh
AU - Niloufar Yazdanpanah
AU - Samaneh Zoghi
AU - Elham Rayzan
AU - Raul Jimenez-Heredia
AU - Anna Segarra-Roca
AU - Kaan Boztug
AU - Nima Rezaei
PY - 2026
DA - 2026/08/03
JO - Journal of medical case reports
DO - 10.1186/s13256-026-06435-8
UR - https://europepmc.org/article/MED/42958346
AB - Background Serine-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 Herein, 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 Next-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.
SN - 1752-1947
ER -