Genetic, Cellular and Clinical Features of ICF Syndrome: a French National Survey

Overview

Journal J Clin Immunol

Publisher Springer

Specialty Allergy & Immunology

Date 2016 Feb 8

PMID 26851945

Citations 29

Authors

Delphine Sterlin

Guillaume Velasco

Despina Moshous

Fabien Touzot

Nizar Mahlaoui

Alain Fischer

Felipe Suarez

Claire Francastel

Capucine Picard

Affiliations

Soon will be listed here.

Abstract

Purpose: Autosomal recessive deficiencies of DNMT3B or ZBTB24 account for two-thirds of cases of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome). This primary immunodeficiency (PID) is characterized mainly by an antibody deficiency, facial abnormalities and centromeric instability. We analyzed the national cohort of patients with ICF syndrome with the aim of providing a more detailed description of the phenotype and management of patients with ICF syndrome.

Methods: Demographic, genetic, immunological, and clinical features were recorded for each patient.

Results: In the French cohort, seven of the nine patients carried DNMT3B mutations, six of which had never been described before. One patient had compound heterozygous ZBTB24 mutations. All patients were found to lack CD19(+)CD27(+) memory B cells. This feature is a major diagnostic criterion for both ICF1 and ICF2. Patients suffered both bacterial and viral infections, and three patients developed bronchiectasis. Autoimmune manifestations (hepatitis, nephritis and thyroiditis) not previously reported in ICF1 patients were also detected in two of our ICF1 patients. The mode of treatment and outcome of the French patients are reported, by genetic defect, and compared with those for 68 previously reported ICF patients. Immunoglobulin (Ig) replacement treatment was administered to all nine French patients. One ICF1 patient presented severe autoimmune manifestations and pancytopenia and underwent allogeneic hematopoietic stem cell transplantation (HSCT), but she died from unknown causes 6 years post-transplant.

Conclusion: Autoimmune signs are uncommon in ICF syndrome, but, when present, they affect patient outcome and require immunosuppressive treatment. The long-term outcome of ICF patients has been improved by the combination of IgG replacement and antibiotic prophylaxis.

Citing Articles

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ZBTB24 is a conserved multifaceted transcription factor at genes and centromeres that governs the DNA methylation state and expression of satellite repeats.

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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.

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The ICF2 gene Zbtb24 specifically regulates the differentiation of B1 cells via promoting heme synthesis.

Gao H, Zhao Y, Zhao S, Dai X, Qin X, Zheng W Cell Mol Biol Lett. 2024; 29(1):123.

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