Investigation of Transcription Factor and Cytokine Gene Expression Levels in Helper T Cell Subsets Among Turkish Patients Diagnosed with ICF2 (Novel ZBTB24 gene Variant) and ICF3 (CDCA7 Variant) Syndrome

• Published in: Journal of clinical immunology 2025-12, Vol.45 (1), p.16-16, Article 16
• Main Authors: Duran, Tugce, Karaselek, Mehmet Ali, Kuccukturk, Serkan, Gul, Yahya, Sahin, Ali, Guner, Sukru Nail, Keles, Sevgi, Reisli, Ismail
• Format: Article
• Language: English
• Subjects: Autosomal recessive inheritance; Biomedical and Life Sciences; Biomedicine; CD19 antigen; CD3 antigen; CD4 antigen; CD8 antigen; Child; Child, Preschool; Cytokines; Cytokines - metabolism; Female; Foxp3 protein; GATA transcription factors; GATA-3 protein; Gene expression; Gene Expression Regulation; genes; Helper cells; heterozygosity; Humans; Hypogammaglobulinemia; ICF syndrome; Immunodeficiency; Immunologic Deficiency Syndromes - diagnosis; Immunologic Deficiency Syndromes - genetics; Immunology; immunosuppression; Infant; Infectious Diseases; interleukin-10; interleukin-4; Internal Medicine; Lymphocytes T; Male; Medical Microbiology; Mutation; Mutation - genetics; Primary Immunodeficiency Diseases - diagnosis; Primary Immunodeficiency Diseases - genetics; Repressor Proteins - genetics; Stat1 protein; Stat3 protein; Stat4 protein; Stat5 protein; Stat6 protein; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-lymphocytes; T-Lymphocytes, Helper-Inducer - immunology; Transcription factors; Transcription Factors - genetics; Turkey
• ISSN: 0271-9142; 1573-2592; 1573-2592
• DOI: 10.1007/s10875-024-01807-5

Immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF), is a rare disease with autosomal recessive inheritance. ICF syndrome. It has been reported that ICF syndrome is caused by mutations in the DNMT3B (ICF1), ZBTB24 (ICF2), CDCA7 (ICF3), and HELLS (ICF4) genes. As a result of literature research, there are no studies on transcription factor and cytokine expressions of helper T cell subsets in ICF syndrome. In the study; Th1 ( TBET , STAT1 , STAT4 ), Th2 ( GATA3 , STAT6 ), Th17 ( RORgt , STAT3 ), Treg ( FoxP3 , STAT5 ) transcription factors and the major cytokines of these cells (Th1; IFNG , Th2; IL4 , Th17; IL17A-21-22 , Treg; IL10 , TGFβ ) expressions were aimed to be evaluated by qRT-PCR. Patients (ICF3: three patients; ICF2: two patients), six heterozygous individual and five healthy controls were included in the study. All patients had hypogammaglobulinemia. Except for the CD19 cells of P2 from patients diagnosed with ICF3, the CD3, CD4, CD8, and CD19 cells in the other ICF3 patients were normal. However, the rates of these cells were low in patients with ICF2 syndrome. Factors belonging to patients’ Th1, Th17 and Treg cells were significantly lower than the control. Additionally, novel mutation was detected in ZBTB24 gene (c.1121–2 A > T). Our study is the first molecular study on Th cell subsets in patients with ICF syndrome and a new mutation that causes ICF2 syndrome has been identified.