Clinical and molecular profile of 17 patients with DOCK8 deficiency: A single-centre experience from Southern India
Bibliographic record
Abstract
Abstract Introduction DOCK8 deficiency is the most common cause of autosomal recessive Hyper IgE syndrome (AR-HIES). The clinical spectrum is wide resulting in combined immunodeficiency, atopy, autoimmunity, and malignancies. Objectives To study the clinical and molecular profile of 17 patients with DOCK8 deficiency. Methods Three hundred sixty patients with various Inborn errors of Immunity (IEIs) were diagnosed in the Pediatric Immunology Unit of our hospital during the study period of February 2017 to April 2023. Based on the clinical and immunological phenotype, DOCK8 deficiency was suspected in 21 patients. Genetic studies confirmed DOCK8 deficiency in 17 patients and their profile was analysed in detail. Results Seventeen patients from 14 kindreds were diagnosed with DOCK8 deficiency. Thirteen of these families (92%) reported consanguinity. Our cohort had eight male and nine females. The mean age at onset of symptoms and diagnosis was seven months and 5.8 years respectively. Eczema was noted in 16 patients. Mucocutaneous manifestations included oromucosal hyperpigmentation(n=6), scalp seborrhoea(n=2), alopecia(n=1) and perianal tag(n=1). The spectrum of infections included pneumonia(n=11), diarrhea (n=5), otitis media (n=4), mucocutaneous candidiasis(n=3),meningoencephalitis(n=2), and cutaneous viral infections (n=3). Two patients had developed bronchiectasis. Autoimmune manifestations were noted in four patients and included autoimmune haemolytic anaemia (n=2) and vasculitis (n=2). Single exonic deletions(n=10) in DOCK8 gene were the most common mutations observed and 13 of these were novel. Twelve patients were on monthly intravenous immunoglobulin therapy at the time of writing this paper. Three patients underwent hematopoietic stem cell transplants elsewhere, two of whom succumbed to post-transplant complications and one is doing well. Overall, eight patients died during the study period, while nine patients continue to remain on follow-up. Conclusion We present one of the largest single-centre experiences on DOCK8 deficiency from India. A significant delay in the diagnosis contributed to poor outcome in our cohort.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".