Primary Ciliary Dyskinesia in First Peoples of Canada
Bibliographic record
Abstract
Chronic respiratory illnesses are common in indigenous populations and are associated with long-term sequelae, including increased bronchiectasis prevalence. While these sequelae are often attributed to antecedent respiratory infections, genetically inherited lung diseases, including primary ciliary dyskinesia (PCD), are seldom considered in indigenous patients. We present three geographically dispersed and unrelated cases of PCD in Canadian First Peoples. [Figure He was diagnosed with complex congenital heart disease (ventricular septal defect, double outlet right ventricle, pulmonary atresia, mitral hypoplasia, but no thoracic/visceral organ laterality defects), and developed chronic cough and nasal congestion shortly after birth. He has chronic ear effusions, recurrent respiratory infections, and persistent atelectasis in the right middle and left lower lobes. Genetic testing revealed homozygous, loss-of-function deletions of exon 5 in DNAL1.Case 2 is an 8-year-old girl with unrelated Mohawk parents from Kahnawake, Quebec, born at 32 weeks gestation, with situs inversus totalis and an atrial septal defect. She had right upper lobe atelectasis and chronic wet cough, and required critical care. Transmission electron microscopic analysis of ciliary axoneme revealed absent outer dynein arms and genetic testing showed homozygous, pathogenic variants in DNAH5 (c.6249G>A). The proband's younger sister and second cousin also have situs inversus totalis, compatible PCD phenotypes, and identical DNAH5 variants. Case 3 is a 56-year-old Inuit woman from Ungava Bay in Nunavik, Quebec with recurrent pneumonias, chronic wet cough and nasal congestion since infancy, and bronchiectasis in the lingula/lower lobes plus right middle lobar collapse. She has situs inversus totalis, conductive hearing loss, pan-sinusitis with polyposis, and several children without fertility assistance. Electron microscopic analysis was normal, but nasal nitric oxide was low (23 nL/min). Genetic testing revealed homozygous, pathogenic, novel variants (c.4095+2C>A), affecting the donor splice site at intron 22 in DNAH11. Discussion: These cases highlight the genetic heterogeneity of PCD within the various First Peoples of Canada, despite some of these sharing common lineages. The different homozygous variants found here illustrate the increased prevalence of autosomal recessive diseases in culturally isolated populations, with increased consanguinity rates, though perhaps unbeknownst to community members. Exploration of these possible founder variants in indigenous communities, including analysis in patients with chronic respiratory disease, bronchiectasis, and/or organ laterality defects, should discover more PCD in these geographically, culturally, and economically isolated peoples.
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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 | 0.002 | 0.003 |
| Science and technology studies | 0.007 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".