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Record W4401735396 · doi:10.14785/lymphosign-2024-0006

Novel variant in <i>IGHM</i> gene in a patient with agammaglobulinemia: A case report of a preschool child presenting with recurrent pneumonia

2024· article· en· W4401735396 on OpenAlexaffvenue
Erin Joy Heifetz, Anahita Dehmoobad Sharifabadi, Rae Brager, Jenny Garkaby

Bibliographic record

VenueLymphoSign Journal · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunodeficiency and Autoimmune Disorders
Canadian institutionsMcMaster University
Fundersnot available
KeywordsX-linked agammaglobulinemiaPrimary immunodeficiencyImmunodeficiencyPneumoniaContext (archaeology)ImmunologyCommon variable immunodeficiencyMedicineAntibodyBiologyPediatricsImmune systemBruton's tyrosine kinaseInternal medicine

Abstract

fetched live from OpenAlex

Introduction: Agammaglobulinemia is a primary immunodeficiency characterized by absent B cells and originates from X-linked or autosomal mutations affecting B cell maturation. While the most common agammaglobulinemia is X-linked, one well-documented site of autosomal recessive agammaglobulinemia is within the immunoglobulin μ heavy chain protein, encoded by the IGHM gene. Such variants frequently result in clinical presentations of recurrent bacterial infections early in life. Aim: To describe a case of a five-year-old female with agammaglobulinemia resulting from a novel homozygous IGHM variant, presenting with pneumonia complicated by empyema and H. influenzae bacteremia. Methods: Case data was compiled retrospectively from the patient’s medical chart, including relevant laboratory testing for immunoglobulins, quantitative B cell subsets, and genetic testing using a primary immunodeficiency panel. Results: The proband is a 5-year-old female with a history of recurrent pneumonia, presenting with H. influenzae bacteremia in the context of pneumonia complicated by an empyema. Investigations revealed low immunoglobulin levels, absent vaccine responses, and undetectable B cells on flow cytometry. Genetic testing revealed a novel homozygous variant in the IGHM gene: c.775T>C, p.Trp259Arg. Conclusion: Autosomal recessive agammaglobulinemia is a rare but severe, treatable disorder of the immune system which typically presents in early childhood. Hypomorphic mutations, while less commonly reported in the literature, are an important consideration in atypical presentations of primary immunodeficiencies, such as in the case presented. Statement of Novelty: Herein, we report a case of agammaglobulinemia presenting with a novel homozygous variant in the IGHM gene leading to later onset agammaglobulinemia in a 5-year-old female.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Case report · Consensus signal: Case report
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.001
Science and technology studies0.0020.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0040.003
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.006
GPT teacher head0.209
Teacher spread0.203 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designCase report
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2024
Admission routes2
Has abstractyes

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