Evidence map›Paper›PMID 39073655›Full record

ArticleJournal of clinical immunology2024

Exclusive Characteristics of the p.E555K Dominant-Negative Variant in Autosomal Dominant E47 Deficiency.

Takanori Utsumi, Miyuki Tsumura, Masato Yashiro, Zenichiro Kato, Kosuke Noma, Fumiaki Sakura, Reiko Kagawa, Yoko Mizoguchi, Shuhei Karakawa, Hidenori Ohnishi and 9 more

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In one paragraph

Article in Journal of clinical immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Takanori UtsumiDepartment of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Miyuki TsumuraDepartment of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Masato YashiroDepartment of Pediatrics, Okayama University Hospital, Okayama, Japan.
Zenichiro KatoDepartment of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.
Kosuke NomaDepartment of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Fumiaki SakuraDepartment of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Reiko KagawaDepartment of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Yoko MizoguchiDepartment of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Shuhei KarakawaDepartment of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Hidenori OhnishiDepartment of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.
Charlotte Cunningham-RundlesDivision of Allergy and Clinical Immunology, Departments of Medicine and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Peter D ArkwrightLydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK.
Masao KobayashiJapanese Red Cross Chugoku-Shikoku Block Blood Center, Hiroshima, Japan.
Hirokazu KaneganeDepartment of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Dusan BogunovicCenter for Inborn Errors of Immunity, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Bertrand BoissonSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
Jean-Laurent CasanovaSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
Takaki AsanoDepartment of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. tasano02@hiroshima-u.ac.jp.
Satoshi OkadaDepartment of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. sokada@hiroshima-u.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTranscription factor 3 (TCF3) encodes 2 transcription factors generated by alternative splicing, E12 and E47, which contribute to early lymphocyte differentiation. In humans, autosomal dominant (AD) E47 transcription factor deficiency is an inborn error of immunity characterized by B-cell deficiency and agammaglobulinemia. Only the recurrent de novo p.E555K pathogenic variant has been associated with this disease and acts via a dominant-negative (DN) mechanism. In this study, we describe the first Asian patient with agammaglobulinemia caused by the TCF3 p.E555K variant and provide insights into the structure and function of this variant.

methodsTCF3 variant was identified by inborn errors of immunity-related gene panel sequencing. The variant E555K was characterized by alanine scanning of the E47 basic region and comprehensive mutational analysis focused on position 555.

resultsThe patient was a 25-year-old male with B-cell deficiency, agammaglobulinemia, and mild facial dysmorphic features. We confirmed the diagnosis of AD E47 transcription factor deficiency by identifying a heterozygous missense variant, c.1663 G>A; p.E555K, in TCF3. Alanine scanning of the E47 basic region revealed the structural importance of position 555. Comprehensive mutational analysis focused on position 555 showed that only the glutamate-to-lysine substitution had a strong DN effect. 3D modeling demonstrated that this variant not only abolished hydrogen bonds involved in protein‒DNA interactions, but also inverted the charge on the surface of the E47 protein.

conclusionsOur study reveals the causative mutation hotspot in the TCF3 DN variant and highlights the weak negative selection associated with the TCF3 gene.

Indexed as

AgammaglobulinemiaBasic Helix-Loop-Helix ProteinsB-LymphocytesAdultDNA Mutational AnalysisGenes, DominantGenetic Predisposition to DiseaseHumansMaleModels, MolecularMutation, MissenseBasic Helix-Loop-Helix ProteinsTCF3 protein, humanAgammaglobulinemiaB-cell deficiencyDominant-negativeE47E555KTCF3

Identifiers

PMID39073655
PMCPMC11286708

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.