Published in:
01-05-2021 | Letter to Editor
Inherited TOP2B Mutation: Possible Confirmation of Mutational Hotspots in the TOPRIM Domain
Authors:
Melinda Erdős, Árpád Lányi, György Balázs, Jean-Laurent Casanova, Bertrand Boisson, László Maródi
Published in:
Journal of Clinical Immunology
|
Issue 4/2021
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Excerpt
B cell deficiencies as immunological phenotypes of human diseases have long been assigned to X-liked or autosomal recessive monogenic variants affecting the expression of the pre-B cell receptor (pre-BCR) or pre-BCR signaling [
1]. The prototypical example is X-linked agammaglobulinemia (XLA), which is characterized by markedly reduced B cells and was first described by Bruton in 1952 [
2]. Autosomal recessive etiologies of agammaglobulinemia include μ heavy chain deficiency (
IGHM), λ5 deficiency (
IGLL1), Igα deficiency (
CD79A), Igβ deficiency (
CD79B), BLNK deficiency (
BLNK), p110δ deficiency (
PIK3CD), p85 deficiency (
PIK3R1), E47 transcription factor deficiency (
TCF3), and SLC39A7 (ZIP7) deficiency (
SLC39A7) [
3]. Autosomal dominant etiology has also been reported, including E47 transcription factor (
TCF3) mutation [
3]. Most recently, heterozygous mutations were reported in
TOP2B, which encodes a type II β DNA topoisomerase that regulates DNA topology and mitigates topological stress during DNA replication and gene transcription [
4]. Only ten patients with TOP2B-mediated immunodeficiency have been published in the medical literature since 2001; all of them had dominant-negative mutations affecting TOPRIM, the DNA gating domain of TOP2B [
4‐
9]. Delays in diagnosis are common in this disease which results in remarkably associated morbidity. …