Abstract 14317: The Prevalence of Motile Ciliary Gene Variants in Children With Transposition of the Great Arteries and Tetralogy of Fallot
Bibliographic record
Abstract
Introduction: Motile ciliary dysfunction plays a central role in the pathogenesis of respiratory abnormalities and congenital heart disease (CHD). The role of ciliary gene variants in the non-heterotaxic CHD population is not well characterised. Methods: This single-centre retrospective cohort study aimed to determine the prevalence of Primary Ciliary Dyskinesia (PCD) gene variants in children with isolated Transposition of the Great Arteries (TGA) and Tetralogy of Fallot (TOF). Patients with whole genome sequencing between 2008-2018 were included. We identified pathogenic (P) or likely pathogenic (LP) single-nucleotide variants (SNVs) and short insertion/deletions (indels) in coding regions of 45 genes known to cause PCD. Patient characteristics and associated respiratory outcomes were evaluated from chart reviews. Results: PCD gene variants were found in 2.9% (5/172) TGA and 3.8% (10/264) TOF patients. Thirteen probands were heterozygous for P/LP SNVs/ indels; CCDC40 N=6, DNAH11 N=2, SPAG1 N=2 and one each of DNAH8/DNAAF1/ARMC4. Two were compound heterozygotes for variants in DNAH11 and DNAH8. At last follow-up, mean age was 14.5 years (SD 6.8, 57.9% male) and 7 deaths had occurred. Asthma was diagnosed in 10.5% TGAs and 8.1% TOFs with 3.9% and 7.3% respectively requiring hospitalisation for primary respiratory illness. In the variant positive subgroup, 5/15 had respiratory abnormalities - bronchiectasis (N = 1), asthma (N = 2), neonatal cough (N = 1), ventilator-associated pneumonia (N = 2). Additional cardiac anomalies occurred in 53% (8/15) - abnormal systemic veins (N = 3), situs inversus, dextrocardia (N = 1), right arch (N = 5), hypoplastic right ventricle (N = 1). An abnormal coronary pattern was seen in 4/5 TGAs. Vaginal and renal agenesis each occurred in 1 patient. Conclusions: Our findings suggest a high prevalence and potential association of ciliary gene variants with respiratory outcomes and situs anomalies in non-heterotaxy CHD.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".