Primary Ciliary Dyskinesia 7

Mendelian MONDO:0012748 Pathograph 19 Show in embeddings browser Primary Ciliary Dyskinesia Ciliopathy

Primary ciliary dyskinesia 7 (CILD7) is the form of primary ciliary dyskinesia (PCD) caused by biallelic loss-of-function variants in DNAH11. DNAH11 encodes a beta-type heavy chain of the axonemal outer dynein arm. In human respiratory cilia it is found only in the proximal part of the axoneme, where it defines the proximal (type 1) outer dynein arm; its paralogue DNAH9 occupies the distal part. The hallmark of CILD7 is a ciliary ultrastructure that looks normal on standard transmission electron microscopy. Electron tomography and immunofluorescence show the real lesion: loss of DNAH11 and a partial reduction of outer dynein arm volume confined to the proximal cilium. The cilia are not immotile. They beat with a stiff, non-flexible, reduced-amplitude and often hyperkinetic (fast) pattern, and some patients have immotile cilia. Clearance fails all the same, giving chronic oto-sino-pulmonary disease and bronchiectasis. Neonatal respiratory distress is less common than in outer dynein arm defect PCD. The mouse orthologue is left-right dynein, mutated in the inversus viscerum (iv) mouse, and about half of patients have situs inversus. Because standard electron microscopy is normal, diagnosis depends on nasal nitric oxide, high-speed video microscopy, immunofluorescence and genetic testing. DNAH11 is one of the most common PCD genes in patients of European ancestry.

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1
Inheritance
5
Pathophys.
11
Phenotypes
19
Pathograph
1
Genes
1
Medical Actions
2
Differentials
1
Models
1
References
1
Deep Research
👪

Inheritance

1
Autosomal recessive inheritance HP:0000007
Disease requires biallelic DNAH11 variants. The first patient was homozygous through paternal uniparental disomy of chromosome 7; later patients are mostly compound heterozygous for private variants.
Autosomal recessive inheritance
Show evidence (2 references)
PMID:22184204 SUPPORT Human Clinical
"Of the 58 unrelated patients with PCD with normal ultrastructure, 13 (22%) had two (biallelic) mutations in DNAH11"
Biallelic variants in affected patients.
PMID:12142464 SUPPORT Human Clinical
"We identified a homozygous nonsense mutation (R2852X) in the DNAH11 gene."
Homozygous truncating variant in the first reported patient.
⚙

Pathophysiology

5
Biallelic DNAH11 Loss of Function
Most DNAH11 alleles are nonsense, frameshift or splice variants; all are private. DNAH11 protein is lost from the cilium in patients with loss-of-function alleles.
DNAH11 hgnc:2942 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves DNAH11 (hgnc:2942). hgnc:2942 is a gene from the HUGO Gene Nomenclature Committee.
Genetic context variant_origin: GERMLINE functional_impact_category: LOSS_OF_FUNCTION
minus-end-directed microtubule motor activity GO:0008569 ↓ DECREASED Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves decreased minus-end-directed microtubule motor activity (GO:0008569). GO:0008569 is a molecular function from the Gene Ontology.
Downstream
Proximal Outer Dynein Arm Defect with Normal Standard Ultrastructure
Show evidence (2 references)
PMID:22184204 SUPPORT Human Clinical
"Of the 35 identified mutant alleles, 24 (69%) were nonsense, insertion/deletion or loss-of-function splice-site mutations."
Predominance of loss-of-function alleles.
PMID:26909801 SUPPORT Human Clinical
"IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia and loss of DNAH11 in individuals with PCD with certain loss-of-function DNAH11 mutations."
Protein is lost from patient cilia; normally it sits only proximally.
Proximal Outer Dynein Arm Defect with Normal Standard Ultrastructure
Loss of DNAH11 removes part of the outer dynein arm volume in the proximal cilium only. The defect is too subtle for standard electron microscopy, which reports normal ultrastructure with intact outer arms, but is seen by electron tomography and immunofluorescence.
multiciliated respiratory epithelial cell CL:0005012 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves multiciliated respiratory epithelial cell, annotated with multiciliated epithelial cell (CL:0005012). CL:0005012 is a cell type from the Cell Ontology.
outer dynein arm GO:0036157 Gene Ontology (GO) Relation: this pathophysiological event involves this cellular component This pathophysiological event involves outer dynein arm (GO:0036157). GO:0036157 is a cellular component from the Gene Ontology.
Downstream
Stiff Hyperkinetic Ciliary Beating with Reduced Bending
Proximal outer dynein arm deficiency
Show evidence (3 references)
PMID:26909801 SUPPORT Human Clinical
"DNAH11 mutations result in a subtle ODA defect in only the proximal region of respiratory cilia, which is detectable by IFM and TEM tomography."
The proximal-only outer arm defect.
PMID:29467202 SUPPORT Human Clinical
"Within this region, electron tomography indicated a deficiency of >25% of proximal outer dynein arm volume in all patients with DNAH11 mutations (n=7)"
Independent tomography quantification of the proximal defect.
PMID:18022865 SUPPORT Human Clinical
"the axonemal ultrastructure of these respiratory cilia was normal and outer dynein arms were intact, as shown by electron microscopy and immunohistochemistry"
Standard electron microscopy is normal.
Stiff Hyperkinetic Ciliary Beating with Reduced Bending
DNAH11-deficient cilia beat with a non-flexible pattern, reduced amplitude and bending capacity (especially proximally) and usually an increased beat frequency. Some patients have immotile cilia.
multiciliated respiratory epithelial cell CL:0005012 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves multiciliated respiratory epithelial cell, annotated with multiciliated epithelial cell (CL:0005012). CL:0005012 is a cell type from the Cell Ontology.
cilium movement GO:0003341 ↕ DYSREGULATED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves dysregulated cilium movement (GO:0003341). GO:0003341 is a biological process from the Gene Ontology.
Animal models
inversus viscerum (iv) Dnah11 mutant mouse Mouse partially recapitulates Normal ultrastructure with abnormal motility, but cilia are static rather than hyperkinetic.
Downstream
Impaired Mucociliary Clearance
Randomization of Left-Right Body Asymmetry
Hyperkinetic stiff ciliary beat
Show evidence (3 references)
PMID:18022865 SUPPORT Human Clinical
"Respiratory ciliated cells from the affected individuals showed an abnormal nonflexible beating pattern with a reduced cilium bending capacity and a hyperkinetic beat."
The characteristic beat abnormality.
PMID:22184204 SUPPORT Human Clinical
"Each of the 14 patients (11 families) with biallelic mutations in DNAH11 that were tested by videomicroscopy had the characteristic hyperkinetic beating pattern and reduced waveform amplitude"
The pattern was present in every tested patient in a larger series.
PMID:22102620 SUPPORT Human Clinical
"Two PCD patients with normal ciliary ultrastructure, one with immotile and one with hyperkinetic cilia were found to carry DNAH11 mutations."
Immotile cilia can also occur.
Impaired Mucociliary Clearance
Abnormal beating fails to clear mucus despite ongoing ciliary motion, giving the same chronic oto-sino-pulmonary disease as other forms of PCD.
mucociliary clearance GO:0120197 ↓ DECREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased mucociliary clearance (GO:0120197). GO:0120197 is a biological process from the Gene Ontology.
respiratory airway UBERON:0001005 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in respiratory airway (UBERON:0001005). UBERON:0001005 is an anatomical location from the Uberon multi-species anatomy ontology.
Animal models
inversus viscerum (iv) Dnah11 mutant mouse Mouse recapitulates Rhinitis, sinusitis and otitis media.
Downstream
Neonatal respiratory distress
Chronic wet cough
Chronic sinusitis
Recurrent otitis media
Conductive hearing impairment
Bronchiectasis
Decreased nasal nitric oxide
Show evidence (1 reference)
PMID:22184204 SUPPORT Human Clinical
"some patients have clinical manifestations of PCD and low levels of nasal nitric oxide, but normal ultrastructure, including a few patients with biallelic mutations in dynein axonemal heavy chain 11 (DNAH11)"
Clinical PCD despite normal ultrastructure in DNAH11 patients.
Randomization of Left-Right Body Asymmetry
The mouse orthologue, left-right dynein, is expressed in the embryonic node and is the gene mutated in iv mice, which have situs inversus in half of homozygotes. DNAH11 patients likewise have randomized situs.
determination of left/right symmetry GO:0007368 ↕ DYSREGULATED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves dysregulated determination of left/right symmetry (GO:0007368). GO:0007368 is a biological process from the Gene Ontology.
Animal models
inversus viscerum (iv) Dnah11 mutant mouse Mouse recapitulates Situs inversus in half of homozygotes.
Downstream
Situs inversus totalis
Situs ambiguus
Show evidence (2 references)
PMID:9353118 SUPPORT Model Organism
"lrd is expressed in the node of the embryo at embryonic day 7.5, consistent with its having a role in LR development."
Nodal expression of the orthologue.
PMID:12142464 SUPPORT Human Clinical
"We conclude that mutations in the coding region of DNAH11 account for situs inversus totalis and probably a minority of cases of PCD."
Situs inversus in human DNAH11 disease.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Primary Ciliary Dyskinesia 7 Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

11
Cardiovascular 1
Situs inversus totalis FREQUENT HP:0001696 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Situs inversus totalis (HP:0001696). HP:0001696 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:12142464 SUPPORT Human Clinical
"We conclude that mutations in the coding region of DNAH11 account for situs inversus totalis and probably a minority of cases of PCD."
Situs inversus totalis in DNAH11 disease.
PMID:18022865 SUPPORT Human Clinical
"We present a German family in which five individuals have PCD and one has KS."
Kartagener syndrome (PCD with situs inversus) in a DNAH11 family.
Ear 2
Recurrent otitis media FREQUENT HP:0000403 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Recurrent otitis media (HP:0000403). HP:0000403 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:22184204 SUPPORT INDIRECT Human Clinical
"chronic otitis media and sinusitis, productive cough, bronchiectasis, situs abnormalities"
Clinical features of the whole normal-ultrastructure PCD group, of which DNAH11 patients were a subset; not reported for DNAH11 patients alone.
PMID:22102620 SUPPORT Model Organism
"This is accompanied by gross rhinitis, sinusitis, and otitis media, all indicators of human PCD."
Otitis media in the Dnah11 mutant mouse.
Conductive hearing impairment HP:0000405 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Conductive hearing impairment (HP:0000405). HP:0000405 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:38891105 SUPPORT INDIRECT REVIEW SYNTHESIS Human Clinical
"Conductive hearing loss has been seen in up to two-thirds of children with PCD"
Review synthesis of PCD cohort studies; the figure is for PCD as a class, so it is applied to DNAH11 disease by inference.
PMID:38891105 SUPPORT INDIRECT REVIEW SYNTHESIS Human Clinical
"No clear genotype-phenotype relationships have emerged regarding sinus disease, ear infections, and hearing loss"
Why a PCD-wide figure is used: hearing loss has not been found to vary by genotype.
Head and Neck 1
Chronic sinusitis VERY_FREQUENT HP:0011109 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Chronic sinusitis (HP:0011109). HP:0011109 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:22184204 SUPPORT INDIRECT Human Clinical
"chronic otitis media and sinusitis, productive cough, bronchiectasis, situs abnormalities"
Clinical features of the whole normal-ultrastructure PCD group, of which DNAH11 patients were a subset; not reported for DNAH11 patients alone.
Respiratory 6
Proximal outer dynein arm deficiency VERY_FREQUENT Dynein arm defect of respiratory motile cilia HP:0012255 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Partial proximal outer dynein arm deficiency, annotated with Dynein arm defect of respiratory motile cilia (HP:0012255). HP:0012255 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:22184204 SUPPORT Human Clinical
"None of the patients with dynein arm or radial spoke/central pair defects, or isolated situs abnormalities, had mutations in DNAH11."
DNAH11 variants were found only in patients whose standard ultrastructure was normal.
PMID:29467202 SUPPORT Human Clinical
"DNAH11 mutations cause a shared abnormality in ciliary ultrastructure previously undetectable by TEM."
The real outer arm defect behind the normal-looking ultrastructure.
Hyperkinetic stiff ciliary beat VERY_FREQUENT Abnormal ciliary motility HP:0012262 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hyperkinetic stiff ciliary beat, annotated with Abnormal ciliary motility (HP:0012262). HP:0012262 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:35305968 SUPPORT Human Clinical
"In DNAH11-mutant cases with normal ultrastructure by TEM, the HSVA revealed stiff and hyperfrequent ciliary beating with low bending capacity in CRC-expanded cells, thereby supporting the diagnosis."
Beat pattern in DNAH11 patient cells.
Neonatal respiratory distress FREQUENT HP:0002643 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Neonatal respiratory distress (HP:0002643). HP:0002643 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:40344341 SUPPORT Human Clinical
"The odds ratio for NRD in the DNAH11 group was significantly lower (OR: 0.35, 95% CI: 0.16-0.76) compared to NRD in the ODA group."
DNAH11-specific comparison.
PMID:40344341 SUPPORT Human Clinical
"38.9% of those with normal ultrastructure associated with DNAH11 variants"
DNAH11-specific frequency.
Chronic wet cough VERY_FREQUENT Productive cough HP:0031245 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Productive cough (HP:0031245), qualified as temporality chronic. HP:0031245 is a phenotype from the Human Phenotype Ontology.
Temporal: CHRONIC
Show evidence (1 reference)
PMID:22184204 SUPPORT INDIRECT Human Clinical
"In patients where ciliary ultrastructure was normal, the clinical phenotype was typical of PCD, including a high prevalence of respiratory distress in full term neonates, chronic otitis media and sinusitis, productive cough, bronchiectasis, situs abnormalities, and infertility"
Clinical features of the whole normal-ultrastructure group, of which DNAH11 patients were a subset; not reported for DNAH11 patients alone.
Bronchiectasis FREQUENT HP:0002110 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Bronchiectasis (HP:0002110). HP:0002110 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:33589394 SUPPORT Human Clinical
"A 17-year-old boy had bronchiectasis and heterozygous mutations in DNAH11. His cilia were motile with normal ultrastructure."
Bronchiectasis with motile, ultrastructurally normal cilia.
Decreased nasal nitric oxide VERY_FREQUENT HP:0033036 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Decreased nasal nitric oxide (HP:0033036). HP:0033036 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:22184204 SUPPORT Human Clinical
"some patients have clinical manifestations of PCD and low levels of nasal nitric oxide, but normal ultrastructure, including a few patients with biallelic mutations in dynein axonemal heavy chain 11 (DNAH11)"
Low nasal NO in DNAH11 patients.
Growth 1
Situs ambiguus OCCASIONAL Heterotaxy HP:0030853 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Heterotaxy (HP:0030853). HP:0030853 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:22184204 SUPPORT Human Clinical
"Most of the 15 families with biallelic mutations had a PCD patient with situs abnormalities (13/15) (Table 2), which probably represents an ascertainment bias."
Situs abnormalities in DNAH11 families; Table 2 of the same paper records individual DNAH11 patients with situs ambiguus (SA). The authors attribute the high proportion partly to ascertainment.
PMID:22184204 SUPPORT INDIRECT BACKGROUND Human Clinical
"Situs inversus totalis occurs in ~50% of patients (Kartagener syndrome) and situs ambiguus occurs in at least 6%."
Frequency of situs ambiguus across PCD as a whole, from the paper's background; no DNAH11-specific frequency was found.
🧬

Genetic Associations

1
DNAH11
Gene: DNAH11 hgnc:2942 gene page HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is DNAH11 (hgnc:2942). hgnc:2942 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: CAUSATIVE variant_origin: GERMLINE
Show evidence (2 references)
PMID:18022865 SUPPORT Human Clinical
"our findings support the view that DNAH11 mutations indeed cause PCD and KS"
Confirmation of DNAH11 as a PCD gene in a multiplex family.
PMID:22184204 SUPPORT Human Clinical
"All mutations were novel and private."
Allelic heterogeneity.
💊

Medical Actions

1
Airway Clearance and Chronic Infection Management
Action: supportive careNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is supportive care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. Ontology label: Supportive Care NCIT:C15747
There is no treatment that restores ciliary function. Management is the supportive care used across primary ciliary dyskinesia: airway clearance, prompt treatment of respiratory infections, and macrolide prophylaxis, for which a randomized trial of azithromycin in PCD reduced pulmonary exacerbations. Nothing in it is specific to DNAH11. The cilia still move, but clearance fails, so the same airway care applies as in immotile-cilia PCD. Curated as a single scoping entry rather than an itemised regimen, because no trial has enrolled by genotype and the umbrella Primary_Ciliary_Dyskinesia entry holds the detailed management block.
Mechanism Target:
Impaired Mucociliary Clearance — Airway clearance techniques substitute mechanically for the mucociliary transport the abnormally beating cilia cannot provide. They do not restore ciliary function.
Show evidence (2 references)
PMID:38891105 SUPPORT INDIRECT REVIEW SYNTHESIS Other
"Though there are no PCD-specific approved therapies that restore ciliary function, routine airway clearance and aggressive management of infections are important to preserve lung health and minimize complications"
The supportive management used across PCD. Applied to DNAH11 disease by inference, since no genotype-stratified treatment evidence exists.
PMID:38891105 SUPPORT INDIRECT REVIEW SYNTHESIS Human Clinical
"A European study found that people with PCD benefitted from treatment with thrice weekly azithromycin, with decreased pulmonary exacerbation rates and without an apparent increase in antibiotic resistance"
The review's summary of a randomized trial in PCD, not stratified by genotype.
🔬

Diagnosis

4
Nasal Nitric Oxide and High-Speed Video Microscopy
Low nasal nitric oxide and the characteristic stiff, hyperkinetic beat on high-speed video microscopy are central to diagnosis, because standard electron microscopy is normal.
Show evidence (2 references)
PMID:35305968 SUPPORT Human Clinical
"In DNAH11-mutant cases with normal ultrastructure by TEM, the HSVA revealed stiff and hyperfrequent ciliary beating with low bending capacity in CRC-expanded cells, thereby supporting the diagnosis."
HSVA supports the diagnosis when TEM is normal.
PMID:27836958 SUPPORT Other
"It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence."
The ERS diagnostic test panel.
Transmission Electron Microscopy and Electron Tomography
Standard TEM is normal and cannot confirm CILD7. Electron tomography detects the proximal outer dynein arm deficiency on existing diagnostic samples.
Show evidence (1 reference)
PMID:29467202 SUPPORT Human Clinical
"Advantageously, electron tomography can be used on existing diagnostic samples and establishes a structural abnormality where ultrastructural studies were previously normal."
Tomography as an adjunct when TEM is normal.
Immunofluorescence Staining for DNAH11
Loss of DNAH11 from the proximal cilium on immunofluorescence supports the diagnosis.
Show evidence (1 reference)
PMID:33589394 SUPPORT Human Clinical
"The loss of DNAH11 proteins at the proximal region of cilia was revealed by IF."
Immunofluorescence finding in a DNAH11 patient.
Genetic Testing
Sequencing of DNAH11 establishes the diagnosis in patients with a PCD phenotype and normal ultrastructure.
Show evidence (1 reference)
PMID:22184204 SUPPORT Human Clinical
"Mutations in DNAH11 are a common cause of PCD in patients without ciliary ultrastructural defects; thus, genetic analysis can be used to ascertain the diagnosis of PCD in this challenging group of patients."
Role of genetic testing.
📊

Prevalence

1
PCD patients with normal ciliary ultrastructure
Unknown
No population prevalence exists for CILD7. DNAH11 explained 22% of unrelated PCD patients with normal ultrastructure in one large referral cohort, and DNAH5 and DNAH11 together account for about half of genetically solved families of white European ancestry. These are shares of selected PCD cohorts, not population rates.
Show evidence (2 references)
PMID:22184204 SUPPORT Human Clinical
"Of the 58 unrelated patients with PCD with normal ultrastructure, 13 (22%) had two (biallelic) mutations in DNAH11"
DNAH11 share within the normal-ultrastructure group.
PMID:31879361 SUPPORT Human Clinical
"white European (52% of families carry DNAH5 or DNAH11 mutations)"
Combined DNAH5/DNAH11 share among European families.
🔀

Differential Diagnoses

2

Conditions with similar clinical presentations that must be differentiated from Primary Ciliary Dyskinesia 7:

Primary Ciliary Dyskinesia 3
Overlapping Features DNAH5 disease gives absent outer dynein arms on standard electron microscopy and immotile cilia.
Primary Ciliary Dyskinesia 40
Overlapping Features DNAH9 encodes the distal beta heavy chain paralogue. Its loss removes distal outer arms, with mild respiratory disease and often normal nasal nitric oxide.
🐁

Animal Models

1
inversus viscerum (iv) Dnah11 mutant mouse
The iv mouse carries a mutation in left-right dynein, the Dnah11 orthologue. Homozygotes have randomized situs, immotile tracheal cilia with normal ultrastructure, reduced sperm motility, rhinitis, sinusitis and otitis media that worsen with age.
Species
Mouse
Genotype
Dnah11 (lrd) iv/iv homozygous
Publication
PMID:22102620
Pathograph links
Randomization of Left-Right Body Asymmetry recapitulates fidelity: high Situs inversus in half of homozygotes.
Show evidence (2 references)
PMID:9353118 SUPPORT Model Organism
"The allelic mouse mutations inversus viscerum (iv) and legless (lgl) produce LR inversion, or situs inversus, in half of live-born homozygotes."
Laterality phenotype of the mutant.
+ 1 more reference
Stiff Hyperkinetic Ciliary Beating with Reduced Bending partially recapitulates fidelity: moderate Normal ultrastructure with abnormal motility, but cilia are static rather than hyperkinetic.
Limitations: Mouse tracheal cilia are immotile, whereas most human DNAH11 patients have hyperkinetic cilia; the static pattern matches only a minority of patients.
Show evidence (1 reference)
PMID:22102620 SUPPORT Model Organism
"We demonstrated immotile tracheal cilia with normal ultrastructure and reduced sperm motility in the Dnahc11(iv) mouse."
Normal ultrastructure with abnormal motility in the mouse.
Impaired Mucociliary Clearance recapitulates fidelity: moderate Rhinitis, sinusitis and otitis media.
Show evidence (1 reference)
PMID:22102620 SUPPORT Model Organism
"This is accompanied by gross rhinitis, sinusitis, and otitis media, all indicators of human PCD."
Upper airway disease in the mouse.
{ }

Source YAML

click to show 
name: Primary Ciliary Dyskinesia 7
creation_date: "2026-10-14T00:00:00Z"
category: Mendelian
disease_term:
  preferred_term: primary ciliary dyskinesia 7
  term:
    id: MONDO:0012748
    label: primary ciliary dyskinesia 7
description: >-
  Primary ciliary dyskinesia 7 (CILD7) is the form of primary ciliary
  dyskinesia (PCD) caused by biallelic loss-of-function variants in DNAH11.
  DNAH11 encodes a beta-type heavy chain of the axonemal outer dynein arm. In
  human respiratory cilia it is found only in the proximal part of the
  axoneme, where it defines the proximal (type 1) outer dynein arm; its
  paralogue DNAH9 occupies the distal part.

  The hallmark of CILD7 is a ciliary ultrastructure that looks normal on
  standard transmission electron microscopy. Electron tomography and
  immunofluorescence show the real lesion: loss of DNAH11 and a partial
  reduction of outer dynein arm volume confined to the proximal cilium. The
  cilia are not immotile. They beat with a stiff, non-flexible,
  reduced-amplitude and often hyperkinetic (fast) pattern, and some patients
  have immotile cilia. Clearance fails all the same, giving chronic
  oto-sino-pulmonary disease and bronchiectasis. Neonatal respiratory
  distress is less common than in outer dynein arm defect PCD. The mouse
  orthologue is left-right dynein, mutated in the inversus viscerum (iv)
  mouse, and about half of patients have situs inversus.

  Because standard electron microscopy is normal, diagnosis depends on nasal
  nitric oxide, high-speed video microscopy, immunofluorescence and genetic
  testing. DNAH11 is one of the most common PCD genes in patients of
  European ancestry.
parents:
- Primary Ciliary Dyskinesia
- Ciliopathy
synonyms:
- CILD7
- ciliary dyskinesia, primary, 7
- primary ciliary dyskinesia 7 with or without situs inversus
- DNAH11-related primary ciliary dyskinesia
notes: >-
  MONDO cross-references this disease as OMIM 611884; 603339 is the DNAH11
  gene record. ClinGen classifies the DNAH11 relationship with this disease
  as Definitive (autosomal recessive). The original family reported that
  DNAH11 nonsense variants were compatible with normal male fertility, while
  the iv mouse has reduced sperm motility, so a human sperm phenotype is not
  asserted here.
references:
- reference: PMID:20301301
  title: "Primary Ciliary Dyskinesia."
  tags:
  - GeneReviews
inheritance:
- name: Autosomal recessive inheritance
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: >-
    Disease requires biallelic DNAH11 variants. The first patient was
    homozygous through paternal uniparental disomy of chromosome 7; later
    patients are mostly compound heterozygous for private variants.
  evidence:
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Of the 58 unrelated patients with PCD with normal ultrastructure, 13 (22%) had two (biallelic) mutations in DNAH11"
    explanation: Biallelic variants in affected patients.
  - reference: PMID:12142464
    reference_title: "Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We identified a homozygous nonsense mutation (R2852X) in the DNAH11 gene."
    explanation: Homozygous truncating variant in the first reported patient.
prevalence:
- population: PCD patients with normal ciliary ultrastructure
  measure_type: UNKNOWN
  notes: >-
    No population prevalence exists for CILD7. DNAH11 explained 22% of
    unrelated PCD patients with normal ultrastructure in one large referral
    cohort, and DNAH5 and DNAH11 together account for about half of
    genetically solved families of white European ancestry. These are shares
    of selected PCD cohorts, not population rates.
  evidence:
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Of the 58 unrelated patients with PCD with normal ultrastructure, 13 (22%) had two (biallelic) mutations in DNAH11"
    explanation: DNAH11 share within the normal-ultrastructure group.
  - reference: PMID:31879361
    reference_title: "Clinical utility of NGS diagnosis and disease stratification in a multiethnic primary ciliary dyskinesia cohort."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "white European (52% of families carry DNAH5 or DNAH11 mutations)"
    explanation: Combined DNAH5/DNAH11 share among European families.
pathophysiology:
- name: Biallelic DNAH11 Loss of Function
  biological_scale: MOLECULAR
  role: trigger
  description: >-
    Most DNAH11 alleles are nonsense, frameshift or splice variants; all are
    private. DNAH11 protein is lost from the cilium in patients with
    loss-of-function alleles.
  genes:
  - preferred_term: DNAH11
    term:
      id: hgnc:2942
      label: DNAH11
  genetic_context:
    variant_origin: GERMLINE
    functional_impact_category: LOSS_OF_FUNCTION
  molecular_functions:
  - preferred_term: minus-end-directed microtubule motor activity
    modifier: DECREASED
    term:
      id: GO:0008569
      label: minus-end-directed microtubule motor activity
  evidence:
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Of the 35 identified mutant alleles, 24 (69%) were nonsense, insertion/deletion or loss-of-function splice-site mutations."
    explanation: Predominance of loss-of-function alleles.
  - reference: PMID:26909801
    reference_title: "DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia and loss of DNAH11 in individuals with PCD with certain loss-of-function DNAH11 mutations."
    explanation: Protein is lost from patient cilia; normally it sits only proximally.
  downstream:
  - target: Proximal Outer Dynein Arm Defect with Normal Standard Ultrastructure
    causal_link_type: DIRECT
- name: Proximal Outer Dynein Arm Defect with Normal Standard Ultrastructure
  biological_scale: CELLULAR
  role: central_effector
  description: >-
    Loss of DNAH11 removes part of the outer dynein arm volume in the proximal
    cilium only. The defect is too subtle for standard electron microscopy,
    which reports normal ultrastructure with intact outer arms, but is seen
    by electron tomography and immunofluorescence.
  cell_types:
  - preferred_term: multiciliated respiratory epithelial cell
    term:
      id: CL:0005012
      label: multiciliated epithelial cell
  cellular_components:
  - preferred_term: outer dynein arm
    term:
      id: GO:0036157
      label: outer dynein arm
  evidence:
  - reference: PMID:26909801
    reference_title: "DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "DNAH11 mutations result in a subtle ODA defect in only the proximal region of respiratory cilia, which is detectable by IFM and TEM tomography."
    explanation: The proximal-only outer arm defect.
  - reference: PMID:29467202
    reference_title: "Primary ciliary dyskinesia with normal ultrastructure: three-dimensional tomography detects absence of DNAH11."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Within this region, electron tomography indicated a deficiency of >25% of proximal outer dynein arm volume in all patients with DNAH11 mutations (n=7)"
    explanation: Independent tomography quantification of the proximal defect.
  - reference: PMID:18022865
    reference_title: "Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused by DNAH11 mutations."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the axonemal ultrastructure of these respiratory cilia was normal and outer dynein arms were intact, as shown by electron microscopy and immunohistochemistry"
    explanation: Standard electron microscopy is normal.
  downstream:
  - target: Stiff Hyperkinetic Ciliary Beating with Reduced Bending
    causal_link_type: DIRECT
  - target: Proximal outer dynein arm deficiency
    causal_link_type: DIRECT
- name: Stiff Hyperkinetic Ciliary Beating with Reduced Bending
  biological_scale: CELLULAR
  role: effector
  description: >-
    DNAH11-deficient cilia beat with a non-flexible pattern, reduced
    amplitude and bending capacity (especially proximally) and usually an
    increased beat frequency. Some patients have immotile cilia.
  cell_types:
  - preferred_term: multiciliated respiratory epithelial cell
    term:
      id: CL:0005012
      label: multiciliated epithelial cell
  biological_processes:
  - preferred_term: cilium movement
    modifier: DYSREGULATED
    term:
      id: GO:0003341
      label: cilium movement
  evidence:
  - reference: PMID:18022865
    reference_title: "Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused by DNAH11 mutations."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Respiratory ciliated cells from the affected individuals showed an abnormal nonflexible beating pattern with a reduced cilium bending capacity and a hyperkinetic beat."
    explanation: The characteristic beat abnormality.
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Each of the 14 patients (11 families) with biallelic mutations in DNAH11 that were tested by videomicroscopy had the characteristic hyperkinetic beating pattern and reduced waveform amplitude"
    explanation: The pattern was present in every tested patient in a larger series.
  - reference: PMID:22102620
    reference_title: "Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Two PCD patients with normal ciliary ultrastructure, one with immotile and one with hyperkinetic cilia were found to carry DNAH11 mutations."
    explanation: Immotile cilia can also occur.
  downstream:
  - target: Impaired Mucociliary Clearance
    causal_link_type: DIRECT
  - target: Randomization of Left-Right Body Asymmetry
    causal_link_type: DIRECT
  - target: Hyperkinetic stiff ciliary beat
    causal_link_type: DIRECT
- name: Impaired Mucociliary Clearance
  biological_scale: TISSUE
  role: effector
  description: >-
    Abnormal beating fails to clear mucus despite ongoing ciliary motion,
    giving the same chronic oto-sino-pulmonary disease as other forms of PCD.
  locations:
  - preferred_term: respiratory airway
    term:
      id: UBERON:0001005
      label: respiratory airway
  biological_processes:
  - preferred_term: mucociliary clearance
    modifier: DECREASED
    term:
      id: GO:0120197
      label: mucociliary clearance
  evidence:
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "some patients have clinical manifestations of PCD and low levels of nasal nitric oxide, but normal ultrastructure, including a few patients with biallelic mutations in dynein axonemal heavy chain 11 (DNAH11)"
    explanation: Clinical PCD despite normal ultrastructure in DNAH11 patients.
  downstream:
  - target: Neonatal respiratory distress
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: Chronic wet cough
    causal_link_type: DIRECT
  - target: Chronic sinusitis
    causal_link_type: DIRECT
  - target: Recurrent otitis media
    causal_link_type: DIRECT
  - target: Conductive hearing impairment
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Bronchiectasis
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Decreased nasal nitric oxide
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
- name: Randomization of Left-Right Body Asymmetry
  biological_scale: ORGANISM
  role: consequence
  description: >-
    The mouse orthologue, left-right dynein, is expressed in the embryonic
    node and is the gene mutated in iv mice, which have situs inversus in
    half of homozygotes. DNAH11 patients likewise have randomized situs.
  biological_processes:
  - preferred_term: determination of left/right symmetry
    modifier: DYSREGULATED
    term:
      id: GO:0007368
      label: determination of left/right symmetry
  evidence:
  - reference: PMID:9353118
    reference_title: "Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "lrd is expressed in the node of the embryo at embryonic day 7.5, consistent with its having a role in LR development."
    explanation: Nodal expression of the orthologue.
  - reference: PMID:12142464
    reference_title: "Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We conclude that mutations in the coding region of DNAH11 account for situs inversus totalis and probably a minority of cases of PCD."
    explanation: Situs inversus in human DNAH11 disease.
  downstream:
  - target: Situs inversus totalis
    causal_link_type: DIRECT
  - target: Situs ambiguus
    causal_link_type: DIRECT
phenotypes:
- category: Cellular
  name: Proximal outer dynein arm deficiency
  description: >-
    Standard TEM is normal; a subtle proximal outer arm deficiency is seen
    only by tomography. Recorded with the closest HPO term for the
    underlying outer dynein arm lesion.
  phenotype_term:
    preferred_term: Partial proximal outer dynein arm deficiency
    term:
      id: HP:0012255
      label: Dynein arm defect of respiratory motile cilia
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "None of the patients with dynein arm or radial spoke/central pair defects, or isolated situs abnormalities, had mutations in DNAH11."
    explanation: DNAH11 variants were found only in patients whose standard ultrastructure was normal.
  - reference: PMID:29467202
    reference_title: "Primary ciliary dyskinesia with normal ultrastructure: three-dimensional tomography detects absence of DNAH11."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "DNAH11 mutations cause a shared abnormality in ciliary ultrastructure previously undetectable by TEM."
    explanation: The real outer arm defect behind the normal-looking ultrastructure.
- category: Cellular
  name: Hyperkinetic stiff ciliary beat
  description: >-
    Stiff, non-flexible beating with reduced amplitude, often at increased
    frequency.
  phenotype_term:
    preferred_term: Hyperkinetic stiff ciliary beat
    term:
      id: HP:0012262
      label: Abnormal ciliary motility
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:35305968
    reference_title: "Analysis of the diagnosis of Japanese patients with primary ciliary dyskinesia using a conditional reprogramming culture."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In DNAH11-mutant cases with normal ultrastructure by TEM, the HSVA revealed stiff and hyperfrequent ciliary beating with low bending capacity in CRC-expanded cells, thereby supporting the diagnosis."
    explanation: Beat pattern in DNAH11 patient cells.
- category: Respiratory
  name: Neonatal respiratory distress
  description: >-
    Less common than in PCD with outer dynein arm defects; reported in about
    39% of DNAH11 patients in a multicentre cohort.
  phenotype_term:
    preferred_term: Neonatal respiratory distress
    term:
      id: HP:0002643
      label: Neonatal respiratory distress
  frequency: FREQUENT
  evidence:
  - reference: PMID:40344341
    reference_title: "The Association of Neonatal Respiratory Distress With Ciliary Ultrastructure and Genotype in Primary Ciliary Dyskinesia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The odds ratio for NRD in the DNAH11 group was significantly lower (OR: 0.35, 95% CI: 0.16-0.76) compared to NRD in the ODA group."
    explanation: DNAH11-specific comparison.
  - reference: PMID:40344341
    reference_title: "The Association of Neonatal Respiratory Distress With Ciliary Ultrastructure and Genotype in Primary Ciliary Dyskinesia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "38.9% of those with normal ultrastructure associated with DNAH11 variants"
    explanation: DNAH11-specific frequency.
- category: Respiratory
  name: Chronic wet cough
  description: Daily wet cough, a core PCD feature.
  phenotype_term:
    preferred_term: Productive cough
    term:
      id: HP:0031245
      label: Productive cough
    temporality: CHRONIC
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    snippet: "In patients where ciliary ultrastructure was normal, the clinical phenotype was typical of PCD, including a high prevalence of respiratory distress in full term neonates, chronic otitis media and sinusitis, productive cough, bronchiectasis, situs abnormalities, and infertility"
    explanation: >-
      Clinical features of the whole normal-ultrastructure group, of which
      DNAH11 patients were a subset; not reported for DNAH11 patients alone.
- category: Respiratory
  name: Chronic sinusitis
  description: Chronic rhinosinusitis.
  phenotype_term:
    preferred_term: Chronic sinusitis
    term:
      id: HP:0011109
      label: Chronic sinusitis
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    snippet: "chronic otitis media and sinusitis, productive cough, bronchiectasis, situs abnormalities"
    explanation: >-
      Clinical features of the whole normal-ultrastructure PCD group, of
      which DNAH11 patients were a subset; not reported for DNAH11 patients
      alone.
- category: Otologic
  name: Recurrent otitis media
  description: Chronic middle ear disease.
  phenotype_term:
    preferred_term: Recurrent otitis media
    term:
      id: HP:0000403
      label: Recurrent otitis media
  frequency: FREQUENT
  evidence:
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    snippet: "chronic otitis media and sinusitis, productive cough, bronchiectasis, situs abnormalities"
    explanation: >-
      Clinical features of the whole normal-ultrastructure PCD group, of
      which DNAH11 patients were a subset; not reported for DNAH11 patients
      alone.
  - reference: PMID:22102620
    reference_title: "Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "This is accompanied by gross rhinitis, sinusitis, and otitis media, all indicators of human PCD."
    explanation: Otitis media in the Dnah11 mutant mouse.
- category: Otologic
  name: Conductive hearing impairment
  description: >-
    Conductive hearing loss from persistent middle ear effusion. Reported for
    PCD as a whole; no DNAH11-specific frequency was found, and no clear
    genotype-phenotype relationship for hearing loss has been described.
  phenotype_term:
    preferred_term: Conductive hearing impairment
    term:
      id: HP:0000405
      label: Conductive hearing impairment
  evidence:
  - reference: PMID:38891105
    reference_title: "Primary Ciliary Dyskinesia: A Clinical Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: "Conductive hearing loss has been seen in up to two-thirds of children with PCD"
    explanation: >-
      Review synthesis of PCD cohort studies; the figure is for PCD as a
      class, so it is applied to DNAH11 disease by inference.
  - reference: PMID:38891105
    reference_title: "Primary Ciliary Dyskinesia: A Clinical Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: "No clear genotype-phenotype relationships have emerged regarding sinus disease, ear infections, and hearing loss"
    explanation: >-
      Why a PCD-wide figure is used: hearing loss has not been found to vary
      by genotype.
- category: Respiratory
  name: Bronchiectasis
  description: >-
    Bronchiectasis develops despite normal-looking ultrastructure. Lung
    function and CT findings in a single-centre comparison did not differ
    significantly from DNAH5 disease.
  phenotype_term:
    preferred_term: Bronchiectasis
    term:
      id: HP:0002110
      label: Bronchiectasis
  frequency: FREQUENT
  evidence:
  - reference: PMID:33589394
    reference_title: "Multifaceted analysis of Japanese cases of primary ciliary dyskinesia: Value of immunofluorescence for ciliary protein detection in patients with DNAH5 and DNAH11 mutations."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A 17-year-old boy had bronchiectasis and heterozygous mutations in DNAH11. His cilia were motile with normal ultrastructure."
    explanation: Bronchiectasis with motile, ultrastructurally normal cilia.
- category: Respiratory
  name: Decreased nasal nitric oxide
  description: >-
    Low nasal nitric oxide is a key diagnostic clue because ultrastructure
    is normal.
  phenotype_term:
    preferred_term: Decreased nasal nitric oxide
    term:
      id: HP:0033036
      label: Decreased nasal nitric oxide
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "some patients have clinical manifestations of PCD and low levels of nasal nitric oxide, but normal ultrastructure, including a few patients with biallelic mutations in dynein axonemal heavy chain 11 (DNAH11)"
    explanation: Low nasal NO in DNAH11 patients.
- category: Cardiovascular
  name: Situs inversus totalis
  description: Mirror-image organ arrangement in a large share of patients.
  phenotype_term:
    preferred_term: Situs inversus totalis
    term:
      id: HP:0001696
      label: Situs inversus totalis
  frequency: FREQUENT
  evidence:
  - reference: PMID:12142464
    reference_title: "Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We conclude that mutations in the coding region of DNAH11 account for situs inversus totalis and probably a minority of cases of PCD."
    explanation: Situs inversus totalis in DNAH11 disease.
  - reference: PMID:18022865
    reference_title: "Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused by DNAH11 mutations."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We present a German family in which five individuals have PCD and one has KS."
    explanation: Kartagener syndrome (PCD with situs inversus) in a DNAH11 family.
- category: Cardiovascular
  name: Situs ambiguus
  description: Heterotaxy occurs in a minority.
  phenotype_term:
    preferred_term: Heterotaxy
    term:
      id: HP:0030853
      label: Heterotaxy
  frequency: OCCASIONAL
  evidence:
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Most of the 15 families with biallelic mutations had a PCD patient with situs abnormalities (13/15) (Table 2), which probably represents an ascertainment bias."
    explanation: >-
      Situs abnormalities in DNAH11 families; Table 2 of the same paper
      records individual DNAH11 patients with situs ambiguus (SA). The
      authors attribute the high proportion partly to ascertainment.
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    quote_role: BACKGROUND
    snippet: "Situs inversus totalis occurs in ~50% of patients (Kartagener syndrome) and situs ambiguus occurs in at least 6%."
    explanation: >-
      Frequency of situs ambiguus across PCD as a whole, from the paper's
      background; no DNAH11-specific frequency was found.
genetic:
- name: DNAH11
  gene_term:
    preferred_term: DNAH11
    term:
      id: hgnc:2942
      label: DNAH11
  relationship_type: CAUSATIVE
  variant_origin: GERMLINE
  notes: >-
    The only gene for CILD7. DNAH11 variants are largely private
    loss-of-function alleles spread across a large 82-exon gene, so a single
    variant on sequencing may reflect a missed second allele.
  gene_disease_validity:
  - validity_classification: DEFINITIVE
    classified_by: CLINGEN
    external_id: CGGV:assertion_84088c46-0763-4ed6-9352-530d846e8b24-2021-10-25T190427.941Z
    evidence:
    - reference: CGGV:assertion_84088c46-0763-4ed6-9352-530d846e8b24-2021-10-25T190427.941Z
      reference_title: "DNAH11 / primary ciliary dyskinesia 7 (Definitive)"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "DNAH11 | HGNC:2942 | primary ciliary dyskinesia 7 | MONDO:0012748 | AR | Definitive"
      explanation: ClinGen Motile Ciliopathy GCEP classifies DNAH11 / primary ciliary dyskinesia 7 as Definitive (AR).
  evidence:
  - reference: PMID:18022865
    reference_title: "Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused by DNAH11 mutations."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "our findings support the view that DNAH11 mutations indeed cause PCD and KS"
    explanation: Confirmation of DNAH11 as a PCD gene in a multiplex family.
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All mutations were novel and private."
    explanation: Allelic heterogeneity.
diagnosis:
- name: Nasal Nitric Oxide and High-Speed Video Microscopy
  description: >-
    Low nasal nitric oxide and the characteristic stiff, hyperkinetic beat on
    high-speed video microscopy are central to diagnosis, because standard
    electron microscopy is normal.
  evidence:
  - reference: PMID:35305968
    reference_title: "Analysis of the diagnosis of Japanese patients with primary ciliary dyskinesia using a conditional reprogramming culture."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In DNAH11-mutant cases with normal ultrastructure by TEM, the HSVA revealed stiff and hyperfrequent ciliary beating with low bending capacity in CRC-expanded cells, thereby supporting the diagnosis."
    explanation: HSVA supports the diagnosis when TEM is normal.
  - reference: PMID:27836958
    reference_title: "European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence."
    explanation: The ERS diagnostic test panel.
- name: Transmission Electron Microscopy and Electron Tomography
  description: >-
    Standard TEM is normal and cannot confirm CILD7. Electron tomography
    detects the proximal outer dynein arm deficiency on existing diagnostic
    samples.
  evidence:
  - reference: PMID:29467202
    reference_title: "Primary ciliary dyskinesia with normal ultrastructure: three-dimensional tomography detects absence of DNAH11."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Advantageously, electron tomography can be used on existing diagnostic samples and establishes a structural abnormality where ultrastructural studies were previously normal."
    explanation: Tomography as an adjunct when TEM is normal.
- name: Immunofluorescence Staining for DNAH11
  description: >-
    Loss of DNAH11 from the proximal cilium on immunofluorescence supports
    the diagnosis.
  evidence:
  - reference: PMID:33589394
    reference_title: "Multifaceted analysis of Japanese cases of primary ciliary dyskinesia: Value of immunofluorescence for ciliary protein detection in patients with DNAH5 and DNAH11 mutations."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The loss of DNAH11 proteins at the proximal region of cilia was revealed by IF."
    explanation: Immunofluorescence finding in a DNAH11 patient.
- name: Genetic Testing
  description: >-
    Sequencing of DNAH11 establishes the diagnosis in patients with a PCD
    phenotype and normal ultrastructure.
  evidence:
  - reference: PMID:22184204
    reference_title: "Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Mutations in DNAH11 are a common cause of PCD in patients without ciliary ultrastructural defects; thus, genetic analysis can be used to ascertain the diagnosis of PCD in this challenging group of patients."
    explanation: Role of genetic testing.
animal_models:
- name: inversus viscerum (iv) Dnah11 mutant mouse
  species: Mouse
  genotype: Dnah11 (lrd) iv/iv homozygous
  publication: PMID:22102620
  description: >-
    The iv mouse carries a mutation in left-right dynein, the Dnah11
    orthologue. Homozygotes have randomized situs, immotile tracheal cilia
    with normal ultrastructure, reduced sperm motility, rhinitis, sinusitis
    and otitis media that worsen with age.
  modeled_mechanisms:
  - target: Randomization of Left-Right Body Asymmetry
    relationship: RECAPITULATES
    fidelity: HIGH
    description: Situs inversus in half of homozygotes.
    evidence:
    - reference: PMID:9353118
      reference_title: "Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "The allelic mouse mutations inversus viscerum (iv) and legless (lgl) produce LR inversion, or situs inversus, in half of live-born homozygotes."
      explanation: Laterality phenotype of the mutant.
    - reference: PMID:9353118
      reference_title: "Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "Here we report the positional cloning of an axonemal dynein heavy-chain gene, left/right-dynein (lrd), that is mutated in both lgl and iv."
      explanation: The mutated gene is the DNAH11 orthologue.
  - target: Stiff Hyperkinetic Ciliary Beating with Reduced Bending
    relationship: PARTIALLY_RECAPITULATES
    fidelity: MODERATE
    description: Normal ultrastructure with abnormal motility, but cilia are static rather than hyperkinetic.
    limitations: >-
      Mouse tracheal cilia are immotile, whereas most human DNAH11 patients
      have hyperkinetic cilia; the static pattern matches only a minority of
      patients.
    evidence:
    - reference: PMID:22102620
      reference_title: "Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "We demonstrated immotile tracheal cilia with normal ultrastructure and reduced sperm motility in the Dnahc11(iv) mouse."
      explanation: Normal ultrastructure with abnormal motility in the mouse.
  - target: Impaired Mucociliary Clearance
    relationship: RECAPITULATES
    fidelity: MODERATE
    description: Rhinitis, sinusitis and otitis media.
    evidence:
    - reference: PMID:22102620
      reference_title: "Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "This is accompanied by gross rhinitis, sinusitis, and otitis media, all indicators of human PCD."
      explanation: Upper airway disease in the mouse.
treatments:
- name: Airway Clearance and Chronic Infection Management
  description: >-
    There is no treatment that restores ciliary function. Management is the
    supportive care used across primary ciliary dyskinesia: airway clearance,
    prompt treatment of respiratory infections, and macrolide prophylaxis,
    for which a randomized trial of azithromycin in PCD reduced pulmonary
    exacerbations. Nothing in it is specific to DNAH11. The cilia still move,
    but clearance fails, so the same airway care applies as in immotile-cilia
    PCD.

    Curated as a single scoping entry rather than an itemised regimen,
    because no trial has enrolled by genotype and the umbrella
    Primary_Ciliary_Dyskinesia entry holds the detailed management block.
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
  target_mechanisms:
  - target: Impaired Mucociliary Clearance
    description: >-
      Airway clearance techniques substitute mechanically for the mucociliary
      transport the abnormally beating cilia cannot provide. They do not
      restore ciliary function.
  evidence:
  - reference: PMID:38891105
    reference_title: "Primary Ciliary Dyskinesia: A Clinical Review."
    supports: SUPPORT
    evidence_source: OTHER
    directness: INDIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: "Though there are no PCD-specific approved therapies that restore ciliary function, routine airway clearance and aggressive management of infections are important to preserve lung health and minimize complications"
    explanation: >-
      The supportive management used across PCD. Applied to DNAH11 disease by
      inference, since no genotype-stratified treatment evidence exists.
  - reference: PMID:38891105
    reference_title: "Primary Ciliary Dyskinesia: A Clinical Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: "A European study found that people with PCD benefitted from treatment with thrice weekly azithromycin, with decreased pulmonary exacerbation rates and without an apparent increase in antibiotic resistance"
    explanation: >-
      The review's summary of a randomized trial in PCD, not stratified by
      genotype.
differential_diagnoses:
- name: Primary Ciliary Dyskinesia 3
  description: >-
    DNAH5 disease gives absent outer dynein arms on standard electron
    microscopy and immotile cilia.
- name: Primary Ciliary Dyskinesia 40
  description: >-
    DNAH9 encodes the distal beta heavy chain paralogue. Its loss removes
    distal outer arms, with mild respiratory disease and often normal nasal
    nitric oxide.
📚

References & Deep Research

References

1
PMID:20301301
Primary Ciliary Dyskinesia.
No top-level findings curated for this source.

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create: Primary Ciliary Dyskinesia 7 (DNAH11) · 2026-10-14T20:30:37Z · View source

New gene-specific entry for CILD7 (MONDO:0012748, DNAH11). Deep research: falcon (Edison) returned 503 'Failed to authenticate' on every attempt, including with --fallback, which did not engage, so the report used is research/Primary_Ciliary_Dyskinesia_7-deep-research-claude_code.md, run directly with the claude_code provider. preflight-dr returned WARN only because the report cites OMIM 603339, the DNAH11 gene record, rather than the phenotype record 611884; the report is about DNAH11 PCD and was used only as a lead. Pathograph: DNAH11 loss of function, then a proximal-only outer dynein arm deficiency that standard TEM misses, then stiff, hyperkinetic beating with reduced bending, then impaired clearance and laterality randomization. iv mouse modelled with a partial-recapitulation caveat (static, not hyperkinetic, cilia). ClinGen Definitive tier copied from the cached CGGV record. Same validation set as PCD3.

Claude Code ▸
Primary Ciliary Dyskinesia 7 (CILD7; DNAH11-related PCD): research report
claude-haiku-5-5, claude-sonnet-5-5 11 citations 2026-10-14T20:13:22.448719

Primary Ciliary Dyskinesia 7 (CILD7; DNAH11-related PCD): research report

Scope and evidence caveat. This report rests on a limited set of web searches that returned mostly abstracts and bibliographic records, so I did not read most full texts. Each claim is tagged as verified in a retrieved source, or as background knowledge that needs checking before curation. Where I have no PMID I give a DOI or URL instead of guessing one. Several clinical sections (treatment, prevention, prognosis) rest on general PCD knowledge, not on DNAH11-specific sources, and are marked as such.

1. Disease information

Overview. CILD7 is an autosomal recessive form of primary ciliary dyskinesia (PCD) caused by biallelic loss-of-function variants in DNAH11, which encodes an axonemal outer dynein arm heavy chain. Its characteristic feature is normal or near-normal ciliary ultrastructure on conventional TEM with abnormal ciliary motility.

  • A 2008 German family had five people with PCD and one with Kartagener syndrome. Their respiratory cilia had normal axonemal structure and intact outer dynein arms, but abnormal beating (Human Mutation 2008, via Geneva archive).
  • GenCC lists the gene-disease validity as Definitive, autosomal recessive. It describes normal ultrastructure with stiff, high-frequency, low-amplitude beating (GenCC SGC-105887.2).
  • The genetic basis was first suggested by Bartoloni et al., PNAS 2002;99(16):10282-6 (doi 10.1073/pnas.152337699; PMC124905). They found DNAH11 variants in a patient with situs inversus totalis and probable Kartagener syndrome. The title says "most likely" PCD, so the PCD link was less firm in that paper (PNAS abstract). The PMID appeared as 12142464 in a QxMD link in the search results, and I did not confirm it.

Identifiers.

Resource ID Source / status
MONDO MONDO:0012748 Seen in the GenCC submission URL, which pairs DNAH11 (HGNC:2942) with MONDO_0012748
OMIM phenotype 611884 From a review table in the search results, with OMIM gene 603339
Disease Ontology DOID:0110605 From a GlyCosmos page
Parent term PCD, MONDO:0016575 From search snippet; verify
HGNC hgnc:2942 From the GenCC URL. The repo uses lowercase hgnc:
ICD-10 / ICD-11 / Orphanet / MeSH not retrieved Check Orphanet for the PCD parent (ORPHA:244) and DNAH11 subtypes

Synonyms. - Ciliary dyskinesia, primary, 7 - CILD7 - DNAH11-related primary ciliary dyskinesia - PCD with normal ultrastructure (an overlapping phenotype description, not a synonym) - Kartagener syndrome, when situs inversus is present

Source type. Disease-level and gene-level resources, plus cohort and family studies. There is no EHR-derived content in what I retrieved.

2. Etiology

  • Causal factor. Biallelic (homozygous or compound heterozygous) pathogenic variants in DNAH11 on 7p21 (OMIM 603339). The disease is purely genetic, with no environmental cause.
  • Genetic risk factors. Only the causal gene is established. Variable severity in siblings with identical genotypes suggests unidentified modifiers. In the Finnish family below, three homozygous siblings had different beat patterns but similar symptom severity (BMC Med Genet 2020, PMC7690114).
  • Environmental modifiers. None specific to DNAH11 retrieved. General PCD knowledge says tobacco smoke and air pollution worsen respiratory outcomes (unverified here).
  • Protective factors and gene-environment interactions. Not identified in the retrieved sources.

3. Phenotypes

The retrieved sources do not give per-phenotype frequencies for DNAH11. Frequencies below are from general PCD knowledge or are qualitative, and should be checked against the HPO annotations and GeneReviews PCD chapter.

Phenotype Suggested HPO term Notes
Chronic or recurrent respiratory infections, from early childhood HP:0002205 Recurrent respiratory infections Described in NORD / MalaCards text
Chronic sinusitis HP:0011109 Chronic sinusitis Same
Bronchiectasis HP:0002110 Bronchiectasis General PCD feature
Chronic wet cough HP:0033709 / HP:0012735 Cough General PCD feature
Recurrent otitis media / conductive hearing loss HP:0000388 Otitis media The mouse model has otitis media
Situs inversus totalis, dextrocardia HP:0001696 / HP:0001651 Variable. Roughly half of PCD patients overall have laterality defects (Bartoloni background). See the Knowles result below
Male infertility / reduced fertility HP:0003251 Male infertility NORD text says reduced fertility; the iv mouse shows reduced sperm motility
Neonatal respiratory distress HP:0002643 General PCD feature; verify
  • Onset. Early childhood, with symptoms often from the neonatal period (general PCD knowledge).
  • Progression. Chronic and slowly progressive lung disease (general PCD knowledge).
  • Quality of life. No DNAH11-specific data retrieved.
  • A point worth encoding. In the Knowles cohort, no patients with dynein arm defects, radial spoke/central pair defects, or isolated situs abnormalities carried DNAH11 mutations (Thorax 2012;67:433).

4. Genetic and molecular information

  • Gene. DNAH11 (hgnc:2942), axonemal dynein heavy chain 11, at 7p21. The original report sequenced all 82 exons.
  • Variants.
  • Reported variants include nonsense, frameshift, splice and missense changes. One early candidate was p.R3004Q (Bartoloni 2002).
  • The Finnish 2020 study reported two novel likely pathogenic variants, one a homozygous missense in a three-sibling family (PMC7690114).
  • I did not retrieve ClinVar or gnomAD data.
  • Functional consequence. Loss of function. By immunofluorescence, DNAH11 is lost in patients with certain loss-of-function mutations (Dougherty et al., below).
  • Gene-disease validity. GenCC lists Definitive (SGC-105887.2). The ClinGen-style curation cited in the Bartoloni search result notes that the variants were collectively reported in fifteen probands in three publications.
  • Frequency among PCD with normal ultrastructure. Knowles et al. sequenced DNAH11 in 163 PCD patients. Of the 58 with normal ultrastructure, 13 (22%) carried two DNAH11 mutations (Thorax 2012). I did not retrieve the PMID.
  • Modifier genes, epigenetics, chromosomal abnormalities. None retrieved. The index patient in Bartoloni et al. had paternal uniparental disomy of chromosome 7 as a mechanism for homozygosity.
  • Origin. Germline.

5. Environmental information

Not applicable as a cause. Infectious agents (e.g., Pseudomonas aeruginosa, Haemophilus influenzae) are secondary colonizers of damaged airways in PCD generally, not DNAH11-specific findings.

6. Mechanism and pathophysiology

Causal chain.

  1. Biallelic loss-of-function variants in DNAH11 reduce or abolish the DNAH11 outer dynein arm heavy chain. This is demonstrated by immunofluorescence (Dougherty et al.).
  2. DNAH11 normally sits only in the proximal region of human respiratory cilia, defining a distinct ODA complex. Its loss causes a subtle, proximal-only ODA defect, seen by IFM and by electron tomography but not by conventional TEM (Dougherty et al.; AJRCMB 2016;55:213, PMID 26909801).
  3. Electron tomography of 7 DNAH11 patients showed more than 25% deficiency of proximal ODA volume in each, invisible on conventional TEM. This comes from a preprint-style record, so treat it as less certain (UCL repository).
  4. The lost dynein force generation leads to abnormal ciliary beating. This is a stiff, static pattern with reduced amplitude and high frequency, with hyperkinetic movement seen in some patients (PMC7690114; GenCC).
  5. Impaired beating gives defective mucociliary clearance. This is inferred from general PCD biology and was not tested in the retrieved DNAH11 papers. It leads to chronic infection, sinusitis, otitis media and bronchiectasis.
  6. Dysfunctional nodal cilia in the embryo lead to randomized left-right asymmetry (situs solitus, inversus or other). Support comes from the mouse ortholog (Supp et al. 1997, Nature 389:963-6, doi 10.1038/40140, PMC1800588). In humans, laterality defects occur in only a subset.
  7. Sperm flagellar dysfunction leads to reduced male fertility (mouse and NORD text).

Cell types and processes. - Ciliated airway epithelial cell: CL:0002145 (verify). - Embryonic node monocilia. - Sperm cell. - Candidate GO terms (verify by lookup before binding): - outer dynein arm assembly (GO:0036158) - cilium movement (GO:0003341) - axonemal dynein complex - determination of left/right symmetry (GO:0007368)

Immune, metabolic, omics, advanced technologies. No DNAH11-specific findings retrieved.

7. Anatomical structures affected

  • Organs. Upper and lower airways (nose, paranasal sinuses, middle ear, bronchi and lungs). Also the male reproductive tract and, variably, the viscera, via laterality defects.
  • Cells and tissue. Ciliated respiratory epithelium (UBERON:0000483 epithelium; verify), the embryonic node, and sperm.
  • Subcellular. Axoneme, outer dynein arm, proximal region of the axoneme (GO:0005858 axonemal dynein complex; verify).
  • Lateralization. Situs inversus totalis or normal situs, as described above.

8. Temporal development

Typical onset is neonatal or early childhood. The course is chronic and lifelong with slow progression. No remission patterns or critical periods were retrieved.

9. Inheritance and population

  • Inheritance. Autosomal recessive (OMIM; GenCC).
  • Prevalence. CILD7 is a minority subset of PCD, which overall is about 1 in 10,000 to 1 in 20,000 (general knowledge, unverified here). DNAH11 explained about 22% of the normal-ultrastructure group in one cohort (Knowles et al.), which was a selected referral population.
  • Consanguinity, founder effects, carrier frequency, sex ratio. Not retrieved. Consanguinity is a known factor in homozygous PCD families generally.
  • Anticipation and germline mosaicism. Not applicable. The uniparental disomy case is noted above.

10. Diagnostics

  • TEM misses it. Conventional electron microscopy shows normal ultrastructure, so a normal TEM does not exclude DNAH11 disease (PMC7690114).
  • High-speed video microscopy (HSVM). Shows a recognizable pattern, described as stiff, with high-frequency, low-amplitude beating. Beat patterns varied even among siblings with the same genotype. A case report suggests HSVM remains useful (PMC12070959).
  • Nasal nitric oxide. That case report found levels are not consistently low in DNAH11 patients, so nNO is not a reliable screen for this subtype (PMC12070959). This contrasts with most other PCD genes, where nNO is usually very low. I only read this from a search summary, so check the full text.
  • Immunofluorescence. Loss of DNAH11 staining is seen with certain loss-of-function mutations (Dougherty et al.).
  • Electron tomography. Detects the proximal ODA deficit, but is a research tool.
  • Genetic testing. Multigene PCD panel or exome sequencing is the practical route. Knowles et al. concluded that genetic analysis can establish the diagnosis in patients without ultrastructural defects.
  • Differential diagnosis. Other PCD genes, cystic fibrosis, immunodeficiency, and secondary ciliary dyskinesia. Consensus guidelines such as the ERS statement were not retrieved.
  • Screening. No newborn screening program exists. Cascade testing of siblings is advisable (general knowledge).

11. Outcome and prognosis

No DNAH11-specific survival or lung-function data were retrieved. Generally, PCD life expectancy is near normal with good care, but bronchiectasis is progressive. The Finnish family study suggests beat-pattern differences do not map neatly onto severity (PMC7690114).

12. Treatment

No disease-specific or DNAH11-specific trials were retrieved. Standard PCD care (unverified in this search) is: - airway clearance physiotherapy (NCIT:C15302 Physical Therapy; verify the appropriate term) - prompt antibiotic treatment of infections (NCIT:C15986 Pharmacotherapy) - ENT management, including hearing support - fertility counseling and assisted reproduction for males - lung transplantation in end-stage disease (NCIT:C15289 Organ Transplantation)

Gene or RNA therapies are not established for DNAH11. Check ClinicalTrials.gov for current trials before curation.

13. Prevention

  • Genetic counseling. Carrier parents have a 25% recurrence risk per pregnancy, and prenatal or preimplantation testing is possible once the variants are known (NCIT:C15240 Genetic Counseling).
  • Tertiary prevention. Vaccination, early infection treatment and avoidance of smoke (general knowledge).

14. Other species and natural disease

I did not find OMIA data. The mouse is the main comparative resource. The inversus viscerum mouse is described under Section 15.

15. Model organisms

  • Mouse, Dnah11 (also written Dnahc11 / lrd), inversus viscerum (iv) and legless (lgl) alleles.
  • Supp et al. 1997 identified left/right-dynein as the mutated gene (Nature 389:963, PMC1800588).
  • Lucas et al. 2012 (Southampton) reported the iv mouse has immotile tracheal cilia with normal ultrastructure, reduced sperm motility, and rhinitis, sinusitis and otitis media (Southampton repository). This makes it a close match to human CILD7.
  • A Dnah11 reporter knock-in showed expression in nodal cilia (MGI assay record, 2020).
  • I found no evidence in these searches of hydrocephalus in Dnah11 mutants.
  • GFP-tagged left-right dynein mice. These confirmed proximal DNAH11 localization in tracheal cilia (Dougherty et al.).
  • Not retrieved. Zebrafish, other organisms, IMPC or MGI phenotype lists, and iPSC or air-liquid-interface culture models. Search MGI and ZFIN before curating any animal_models: entry.

Key references

Reference Identifier Note
Bartoloni et al., PNAS 2002;99:10282-6 doi 10.1073/pnas.152337699; PMC124905 PMID likely 12142464, unconfirmed
Supp et al., Nature 1997;389:963-6 doi 10.1038/40140; PMC1800588 PMID not retrieved
Schwabe et al., Hum Mutat 2008 Geneva archive PMID not retrieved
Knowles et al., Thorax 2012;67:433-41 doi 10.1136/thoraxjnl-2011-200301 PMID not confirmed. One candidate seen in results was wrong, so look it up before use
Dougherty et al., AJRCMB 2016;55:213-24 PMID 26909801 Reported in search summary
Finnish families, BMC Med Genet 2020 PMC7690114 Two novel variants; beat-pattern variability
DNAH11 case report PMC12070959 Normal-range nNO reported; HSVM useful
Shoemark et al., electron tomography UCL repository (preprint-style record) Proximal ODA deficit
GenCC SGC-105887.2 Definitive, AR

Gaps to close before curation. - Confirm all PMIDs by running just fetch-reference on each one. - Resolve ontology terms by lookup, not from the suggestions above. - Read the GeneReviews PCD chapter for the baseline phenotype and frequencies. - Check the ClinGen assertion for DNAH11 and PCD. - Look up Orphanet and the ICD codes.

Sources: - GenCC submission SGC-105887.2 - Thorax 2012 Knowles et al. - BMC Med Genet 2020, PMC7690114 - Case report, PMC12070959 - UCL tomography record - Dougherty et al. 2016 - Bartoloni et al. 2002 - Supp et al. 1997 - Southampton iv mouse record - Human Mutation 2008, Geneva archive - NORD CILD7 page

Reference Validation

Checked with linkml-reference-validator 0.3.0.

Outcome Count
References checked 8
Resolved 8
Unresolved (possible confabulation) 0
Unverifiable 0
References weighed for topical relevance 8
On topic 5
Off topic 0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 25
Resolved 23
Unresolved (possible confabulation) 0
Obsolete 0
Unverifiable 2
Terms whose name was checked 7
Terms named correctly 4
Terms named as a different term 3

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

  • MONDO:0012748 (1 mention) - the report calls it "MONDO"; MONDO calls it primary ciliary dyskinesia 7
  • DOID:0110605 (1 mention) - the report calls it "Disease Ontology"; DOID calls it primary ciliary dyskinesia 7
  • CL:0002145 (1 mention) - the report calls it "verify"; CL calls it multiciliated columnar cell of tracheobronchial tree

Prefixes with no resolver

Terms carrying these prefixes were not checked either way, because no configured ontology covers them. An unrecognised prefix may name an ontology this run could not reach as easily as one that does not exist, so nothing here is evidence of fabrication: ORPHA.