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Progressive Immunodeficiency with Gradual Depletion of B and CD4+ T Cells in Immunodeficiency, Centromeric Instability and Facial Anomalies Syndrome 2 (ICF2)

1
Department of Clinical Immunology and Rheumatology, Hannover Medical School, 30625 Hannover, Germany
2
Department of Human Genetics, Hannover Medical School, 30625 Hannover, Germany
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Institute of Pathology, Hannover Medical School, 30625 Hannover, Germany
4
Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
5
Department of Paediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, 30625 Hannover, Germany
*
Author to whom correspondence should be addressed.
Diseases 2019, 7(2), 34; https://doi.org/10.3390/diseases7020034
Received: 4 March 2019 / Revised: 2 April 2019 / Accepted: 4 April 2019 / Published: 4 April 2019
(This article belongs to the Section Immunology)
Immunodeficiency, centromeric instability and facial anomalies syndrome 2 (ICF2) is a rare autosomal recessive primary immunodeficiency disorder. So far, 27 patients have been reported. Here, we present three siblings with ICF2 due to a homozygous ZBTB24 gene mutation (c.1222 T>G, p. (Cys408Gly)). Immune deficiency in these patients ranged from late-onset combined immunodeficiency (CID) with severe respiratory tract infections and recurrent shingles to asymptomatic selective antibody deficiency. Evident clinical heterogeneity manifested despite a common genetic background, suggesting the pathogenic relevance of epigenetic modification. Immunological follow-up reveals a previously unidentified gradual depletion of B and CD4+ T cells in all three presented patients with transition of a common variable immunodeficiency (CVID)-like disease to late-onset-CID in one of them. Considering all previously published cases with ICF2, we identify inadequate antibody responses to vaccines and reduction in CD27+ memory B cells as prevalent immunological traits. High mortality among ICF2 patients (20%) together with the progressive course of immunodeficiency suggest that hematopoietic stem cell transplantation (HSCT) should be considered as a treatment option in due time. View Full-Text
Keywords: ICF syndrome; B cell immunodeficiency; T cell immunodeficiency; combined immunodeficiency; ICF2; ZBTB24 ICF syndrome; B cell immunodeficiency; T cell immunodeficiency; combined immunodeficiency; ICF2; ZBTB24
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Sogkas, G.; Dubrowinskaja, N.; Bergmann, A.K.; Lentes, J.; Ripperger, T.; Fedchenko, M.; Ernst, D.; Jablonka, A.; Geffers, R.; Baumann, U.; Schmidt, R.E.; Atschekzei, F. Progressive Immunodeficiency with Gradual Depletion of B and CD4+ T Cells in Immunodeficiency, Centromeric Instability and Facial Anomalies Syndrome 2 (ICF2). Diseases 2019, 7, 34.

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  • Supplementary File 1:

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  • Externally hosted supplementary file 1
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    Link: http://n.a.
    Description: Immunological follow-up of three patients with ICF2
  • Externally hosted supplementary file 2
    Doi: n.a.
    Link: http://n.a.
    Description: Genotype, phenotype, immunological findings, treatment and outcome of all published ICF2 patients.
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