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<i>HYDIN</i> Variants Are a Common Cause of Primary Ciliary Dyskinesia in French Canadians

2022· letter· en· W4296026335 on OpenAlexafffund
Adam J. Shapiro, Guillaume Sillon, Daniela D’Agostino, Laurence Baret, Francesc López‐Giráldez, Shrikant Mane, Margaret W. Leigh, Stephanie D. Davis, Michael R. Knowles, Maimoona A. Zariwala

Bibliographic record

VenueAnnals of the American Thoracic Society · 2022
Typeletter
Languageen
FieldMedicine
TopicCystic Fibrosis Research Advances
Canadian institutionsMcGill University
FundersNational Center for Advancing Translational SciencesNational Human Genome Research InstituteYale UniversityRare Diseases Clinical Research NetworkNational Institutes of HealthMcGill University Health CentreNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteMcGill University
KeywordsPrimary ciliary dyskinesiaMedicineAnnalsDyskinesiaBronchiectasisInternal medicineClassicsLungParkinson's diseaseDisease

Abstract

fetched live from OpenAlex

To the Editor:Primary ciliary dyskinesia (PCD) is a rare genetic disorder resulting in chronic sino-oto-pulmonary infections, bronchiectasis, and organ laterality defects (Online Mendelian Inheritance in Man #244400).Various PCD diagnostic tests are recommended per American Thoracic Society and European Respiratory Society clinical practice guidelines (1, 2), including nasal nitric oxide (nNO) measurement, ciliary ultrastructural analysis on transmission electron microscopy (TEM), ciliary beat pattern analysis with high-speed video microscopy, and genetic testing for PCD-related genes.However, no single diagnostic test detects all forms of PCD.In the past two decades, more than 50 PCD-related genes have been discovered ( 3), but most commercial genetic multigene panels analyze only a portion of these using next-generation sequencing (NGS) techniques.Recently, a known PCD gene, HYDIN (HYDIN axonemal central pair apparatus protein; chromosome 16, NM_001270974.2,Online Mendelian Inheritance in Man #608647), rarely associated with PCD and mostly in consanguineous individuals from the Faroe Islands (c.922A.T [p.Lys308Ter]; ClinVar identifier 39699), was implicated in 8% of suspected European PCD cases with normal organ arrangement (situs solitus) (4).Inherited in an autosomalrecessive pattern and encoding a ciliary protein in the central apparatus, HYDIN is a large gene (85 coding exons, 5,121 amino acids), with biallelic pathogenic variants causing PCD.The phenotypic characteristics are reported as situs solitus, normal results on TEM, and low nNO (5).Presence of the nearly identical pseudogene HYDIN2 (HYDIN axonemal central pair apparatus protein 2; chromosome 1) complicates mutational analysis, as additional steps are necessary to ascertain the identified variants map on HYDIN.Hence, most commercial genetic panels do not include variant analysis of this large, complex, and seemingly rare PCD gene.

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)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.252
Threshold uncertainty score0.507

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0050.002
Scholarly communication0.0010.000
Open science0.0010.000
Research integrity0.0070.004
Insufficient payload (model declined to judge)0.0030.001

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 head0.069
GPT teacher head0.376
Teacher spread0.306 · 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 designObservational
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

Citations16
Published2022
Admission routes2
Has abstractyes

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Same venueAnnals of the American Thoracic SocietySame topicCystic Fibrosis Research AdvancesFrench-language works237,207