👪

Inheritance

1

Autosomal recessive HP:0000007

Reported patients carry homozygous or compound heterozygous DNAH7 variants.

Autosomal recessive inheritance

Show evidence (2 references)

PMID:40810911 SUPPORT Human Clinical

"loss-of-function variants in DNAH7 were identified in two unrelated infertile men with asthenozoospermia through whole exome sequencing, including compound heterozygous variants"

Compound heterozygous biallelic variants fit recessive inheritance.

CGGV:assertion_90a097d6-5127-4466-8c81-00e99dab2696-2025-02-13T170000.000Z SUPPORT Other

ClinGen records autosomal recessive inheritance for DNAH7 and primary ciliary dyskinesia in general.

⚙

Pathophysiology

4

Loss of DNAH7 Inner-Arm Dynein Heavy Chain

Missense variants in conserved residues and truncating variants both reduce DNAH7 protein in patient sperm.

DNAH7 hgnc:18661

minus-end-directed microtubule motor activity GO:0008569 ↓ DECREASED

Inner dynein arm GO:0036156

Downstream

Inner Dynein Arm Loss in the Sperm Flagellum

Inner Dynein Arm Loss in Respiratory Cilia Expected from DNAH7's location in respiratory inner arms; not demonstrated in a patient with known DNAH7 variants.

Show evidence (2 references)

PMID:34476482 SUPPORT Human Clinical

"The expression of DNAH7 in the spermatozoa from the DNAH7-defective patients was significantly decreased"

Reduced DNAH7 protein in patient sperm with missense variants.

PMID:40810911 SUPPORT Human Clinical

"immunofluorescent staining revealed a marked reduction of DNAH7 and other IDA-associated proteins, such as DNAH3 and DNAH6, in the patients' spermatozoa"

Loss of DNAH7 and of other inner-arm heavy chains in patient sperm with truncating variants.

Inner Dynein Arm Loss in the Sperm Flagellum

Transmission electron microscopy shows inner dynein arms missing from patient sperm flagella, while outer-arm proteins are kept. The remaining motors cannot drive normal flagellar beating.

Sperm CL:0000019

Inner dynein arm assembly GO:0036159 ↓ DECREASED Flagellated sperm motility GO:0030317 ↓ DECREASED

Sperm flagellum GO:0036126

Downstream

Absent inner dynein arms in sperm flagella

Multiple morphological abnormalities of the sperm flagella

Reduced sperm motility

Male infertility

Show evidence (4 references)

PMID:34476482 SUPPORT Human Clinical

"The spermatozoa from the patients with DNAH7 bi-allelic mutations showed specific losses in the inner dynein arms."

Inner-arm loss in sperm of men with missense variants.

PMID:40810911 SUPPORT Human Clinical

"transmission electron microscopy results indicated a severe loss of inner dynein arms (IDAs) in the sperm flagella of both patients"

Inner-arm loss in sperm of men with truncating variants.

PMID:35543642 SUPPORT Human Clinical

"The axoneme structure of the sperm from a DNAH7-deficient patient revealed the loss of inner dynein arms."

Inner-arm loss in the sperm of a third independent patient.

+ 1 more reference

Inner Dynein Arm Loss in Respiratory Cilia

In one PCD patient whose respiratory cilia lacked inner dynein arms and moved abnormally, DNAH7 was made in the cell but missing from the cilia. That patient was not genotyped, so the lesion may have been in another gene. The only patient with biallelic DNAH7 variants whose airway cilia were examined, a man homozygous for a frameshift, had normal ciliary ultrastructure on electron microscopy. An inner-arm defect in airway cilia is therefore expected from DNAH7's location but has not been shown in a genotyped CILD50 patient.

Respiratory tract multiciliated cell CL:4030034

Cilium movement GO:0003341 ↓ DECREASED

Inner dynein arm GO:0036156

Downstream

Impaired Mucociliary Clearance

Show evidence (3 references)

PMID:11877439 SUPPORT INDIRECT In Vitro

"In cilia from PCD cells, DNAH7 was undetectable, whereas intracellular DNAH7 was clearly present."

DNAH7 absent from the cilia of a PCD patient lacking inner arms; the patient's genotype was not determined.

PMID:31443223 SUPPORT BACKGROUND Human Clinical

"It was found to be missing in a patient with PCD who had an absence of IDA and displayed abnormal cilia motility, but with normal ODA"

Records that the 2002 patient's cilia moved abnormally as well as lacking inner arms.

PMID:37998386 REFUTE In Vitro

"In addition, we observed normal ciliary ultrastructure in patients with variants in the PCD candidate genes DNAH1 (n = 2) and DNAH7 (n = 1; Figure 4)."

Electron microscopy of nasal brush biopsies from a man homozygous for a DNAH7 frameshift showed no inner-arm loss. It does not exclude a functional inner-arm defect, but it is the only direct look at airway cilia in a genotyped patient, and it found no structural defect.

Impaired Mucociliary Clearance

If respiratory inner arms fail, mucus clearance from the airways falls, as in other PCD forms, leading to chronic sinus and bronchial infection and bronchiectasis. Clearance has not been measured in a CILD50 patient, and the airway phenotypes below rest on very few patients, so this step is inferred from the general PCD mechanism.

Mucociliary clearance GO:0120197 ↓ DECREASED

Downstream

Chronic sinusitis

Chronic bronchitis

Bronchiectasis Repeated airway infection and inflammation damage the bronchial wall.

Show evidence (1 reference)

PMID:34476482 SUPPORT INDIRECT BACKGROUND Human Clinical

"Dynein protein arms play a crucial role in the motility of both the cilia and flagella, and defects in these proteins generally impair the axoneme structure and cause primary ciliary dyskinesia."

General statement that dynein arm defects cause PCD; not a finding in DNAH7 patients.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

7

Genitourinary 4

Male infertility HP:0003251

Show evidence (1 reference)

PMID:40810911 SUPPORT Human Clinical

"loss-of-function variants in DNAH7 were identified in two unrelated infertile men with asthenozoospermia"

Male infertility in patients with truncating variants.

Reduced sperm motility HP:0012207

Show evidence (1 reference)

PMID:34476482 SUPPORT Human Clinical

"we recruited 85 infertile patients with idiopathic asthenozoospermia and identified bi-allelic mutations in DNAH7 (NM_018897.3) from three patients using whole-exome sequencing"

Asthenozoospermia in men with missense variants.

Absent inner dynein arms in sperm flagella Abnormal sperm axoneme morphology HP:0033524

Show evidence (1 reference)

PMID:40810911 SUPPORT Human Clinical

"transmission electron microscopy results indicated a severe loss of inner dynein arms (IDAs) in the sperm flagella of both patients"

Ultrastructural inner-arm loss in patient sperm.

Multiple morphological abnormalities of the sperm flagella Abnormal sperm tail morphology HP:0012868

Show evidence (1 reference)

PMID:35543642 SUPPORT Human Clinical

"we showed that DNAH7 disruption in humans results in male infertility, which was characterised by multiple morphological abnormalities of sperm flagella"

MMAF in a man with DNAH7 disruption.

Head and Neck 1

Chronic sinusitis HP:0011109

Show evidence (2 references)

CGGV:assertion_90a097d6-5127-4466-8c81-00e99dab2696-2025-02-13T170000.000Z SUPPORT REVIEW SYNTHESIS Other

"Some of the most common patient phenotypes are: Absent inner dynein arms, Chronic sinusitis and Chronic bronchitis."

ClinGen's evidence summary for DNAH7 and PCD50 names chronic sinusitis as a common patient phenotype.

PMID:37998386 SUPPORT Human Clinical

"Early onset of chronic wet cough and CRSwNP, parental consanguinity, and P. aeruginosa infection | DNAH7 | c.12056_12060delTATGT c.12056_12060delTATGT | p.(Leu4019Serfs*3)"

Table 1 row for the patient homozygous for a DNAH7 frameshift. CRSwNP is defined in the table footnote as chronic rhinosinusitis with nasal polyps.

Immune 1

Chronic bronchitis HP:0004469

Show evidence (1 reference)

CGGV:assertion_90a097d6-5127-4466-8c81-00e99dab2696-2025-02-13T170000.000Z SUPPORT REVIEW SYNTHESIS Other

"Some of the most common patient phenotypes are: Absent inner dynein arms, Chronic sinusitis and Chronic bronchitis."

ClinGen's evidence summary for DNAH7 and PCD50 names chronic bronchitis as a common patient phenotype.

Respiratory 1

Bronchiectasis HP:0002110

Show evidence (2 references)

PMID:37998386 SUPPORT Human Clinical

"At inclusion in our study, all patients had bronchiectasis without a definite diagnosis of PCD."

The cohort, which included the DNAH7 patient, was selected for bronchiectasis.

PMID:37998386 SUPPORT Human Clinical

"Early onset of chronic wet cough and CRSwNP, parental consanguinity, and P. aeruginosa infection | DNAH7 | c.12056_12060delTATGT c.12056_12060delTATGT | p.(Leu4019Serfs*3)"

Identifies the DNAH7 patient within the bronchiectasis cohort and his airway history.

🧬

Genetic Associations

1

DNAH7 (Causal)

Gene: DNAH7 hgnc:18661 gene page

Show evidence (6 references)

PMID:34476482 SUPPORT Human Clinical

"Our study is the first to demonstrate that bi-allelic mutations in DNAH7 may impair the integrality of axoneme structure, affect sperm motility, and cause asthenozoospermia in humans."

First human genetic report for DNAH7.

PMID:40810911 SUPPORT Human Clinical

"our findings confirmed that DNAH7 variants may contribute to asthenozoospermia by affecting flagellar IDA assembly"

Independent replication with truncating alleles.

PMID:35543642 SUPPORT Human Clinical

"Thus, DNAH7 is critical for axoneme and mitochondrial development in human sperm."

A third report of DNAH7 loss of function in an infertile man.

+ 3 more references

💊

Medical Actions

2

Intracytoplasmic Sperm Injection

Action: Intracytoplasmic Sperm Injection NCIT:C185482

Platform: Other

ICSI bypasses the motility defect. Patients in all three sperm genetic reports fathered children or achieved pregnancies through ICSI.

Mechanism Target:

Inner Dynein Arm Loss in the Sperm Flagellum — Direct injection makes flagellar motility irrelevant to fertilization.

Show evidence (1 reference)

PMID:40810911 SUPPORT Human Clinical

"the infertility of the patients harboring DNAH7 mutations could be successfully overcome by intracytoplasmic sperm injection treatment"

ICSI success in patients with truncating variants.

Show evidence (2 references)

PMID:34476482 SUPPORT Human Clinical

"these patients were able to have their children via intra-cytoplasmic sperm injection treatment"

ICSI success in patients with missense variants.

PMID:35543642 SUPPORT Human Clinical

"Live birth was achieved via intracytoplasmic sperm injection."

ICSI success in the patient with MMAF.

Airway Clearance and Chronic Infection Management

Action: supportive care Ontology label: Supportive Care NCIT:C15747

Platform: Other

There is no treatment for the ciliary defect. Patients with airway disease receive the supportive care used across primary ciliary dyskinesia: airway clearance, prompt treatment of infections, and surveillance of lung function. Nothing in it is DNAH7-specific.

Mechanism Target:

Impaired Mucociliary Clearance — Airway clearance techniques substitute mechanically for the mucus transport the cilia cannot provide, and antibiotics treat the infections that follow. Neither restores ciliary function.

Show evidence (1 reference)

PMID:38891105 SUPPORT REVIEW SYNTHESIS Human Clinical

"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"

Review statement of standard PCD airway management. It covers PCD in general and is not specific to DNAH7.

🔬

Diagnosis

1

Exome Sequencing in Asthenozoospermia

All reported patients were found by exome sequencing of infertile men with asthenozoospermia, supported by sperm electron microscopy showing inner-arm loss and immunostaining showing missing DNAH7.

Whole exome sequencing NCIT:C101295

Show evidence (1 reference)

PMID:34476482 SUPPORT Human Clinical

"identified bi-allelic mutations in DNAH7 (NM_018897.3) from three patients using whole-exome sequencing"

Diagnostic route in the founding report.

🔀

Differential Diagnoses

1

Conditions with similar clinical presentations that must be differentiated from Primary Ciliary Dyskinesia 50:

{ }

Source YAML

click to show

name: Primary Ciliary Dyskinesia 50
creation_date: "2026-10-14T00:00:00Z"
category: Mendelian
synonyms:
- CILD50
- ciliary dyskinesia, primary, 50
- DNAH7-related primary ciliary dyskinesia
description: >-
  Primary ciliary dyskinesia 50 (CILD50) is the autosomal recessive disorder
  attributed to biallelic variants in DNAH7, which encodes an axonemal inner
  dynein arm heavy chain. In human respiratory cilia DNAH7 is the heavy chain
  of the single-headed inner arms IDAb and IDAe and runs along the whole
  axoneme. It was first identified in 2002 as the protein missing from the
  cilia of a PCD patient whose cilia lacked inner dynein arms; that patient's
  DNAH7 was made in the cell but not built into the cilium, and the gene was
  not sequenced.

  Most of the human genetic evidence comes from sperm. Three Chinese
  studies found biallelic DNAH7 variants in six infertile men with
  asthenozoospermia: three with missense variants among 85 men screened, one
  with a loss-of-function variant and multiple morphological abnormalities
  of the sperm flagella (MMAF), and two with compound heterozygous
  truncating variants. Sperm flagella lacked inner dynein arms and DNAH7
  protein. In the truncating cases, the inner-arm heavy chains DNAH3 and
  DNAH6 were also reduced, while outer-arm proteins were normal. ICSI gave
  pregnancies and live births.

  The airway evidence is thinner. OMIM and the ClinGen curation describe
  chronic sinusitis and chronic bronchitis as features of CILD50, attributed
  to the 2021 patients, but the abstract of that report does not mention
  them. The one genotyped patient with documented airway disease is a
  51-year-old Turkish man, homozygous for a DNAH7 frameshift, with
  bronchiectasis, early-onset chronic wet cough, chronic rhinosinusitis with
  nasal polyps and Pseudomonas aeruginosa infection. His nasal nitric oxide
  was above the diagnostic threshold, his ciliary ultrastructure on
  electron microscopy was normal, and he was classified as possible PCD. A
  Portuguese child with Kartagener syndrome carried DNAH7 missense variants,
  but also two truncating DNAH5 variants that are the more likely cause. No
  laterality defect has been reported with DNAH7 variants alone.

  CILD50 is therefore named as primary ciliary dyskinesia from DNAH7's place
  in respiratory cilia, the 2002 biochemical case, and a small number of
  patients with airway disease. The best established human phenotype is
  male infertility from an inner-arm sperm defect. ClinGen rates DNAH7 as
  Limited for primary ciliary dyskinesia.
parents:
- Primary Ciliary Dyskinesia
- Ciliopathy
notes: >-
  MONDO (MONDO:0957252, OMIM 620356 cross-reference) names this entity as a
  form of primary ciliary dyskinesia. The OMIM definition, as reproduced by
  NCBI MedGen (C5830473), reads "Primary ciliary dyskinesia-50 (CILD50) is
  characterized by chronic sinusitis and bronchitis as well as male
  infertility", citing Wei et al. 2021 (PMID:34476482) and Gao et al. 2022
  (PMID:35543642). OMIM has no fetcher in this repository, so it is not
  cited as evidence. The PMID:34476482 full text is not in PubMed Central
  and the publisher copy is not open access; its cached record is the
  abstract only, which reports no airway symptoms, so the clinical details
  of those three men cannot be quoted here. The chronic sinusitis and
  chronic bronchitis phenotypes are instead sourced from the ClinGen
  evidence summary and from the one patient with tabulated clinical detail
  (PMID:37998386), and should be read as reported in very few patients. The
  umbrella
  Primary_Ciliary_Dyskinesia entry lists CILD50 as a has_subtypes row. ClinGen
  classified DNAH7 against primary ciliary dyskinesia (MONDO:0016575), not
  this numbered entity, so no gene_disease_validity assertion is recorded on
  the genetic row; the ClinGen row is quoted as evidence instead. No
  GeneReviews chapter covers CILD50 specifically (just check-genereviews).
  No Dnah7 animal model was found in the cached literature.
inheritance:
- name: Autosomal recessive
  description: >-
    Reported patients carry homozygous or compound heterozygous DNAH7
    variants.
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  evidence:
  - reference: PMID:40810911
    reference_title: "Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "loss-of-function variants in DNAH7 were identified in two unrelated infertile men with asthenozoospermia through whole exome sequencing, including compound heterozygous variants"
    explanation: Compound heterozygous biallelic variants fit recessive inheritance.
  - reference: CGGV:assertion_90a097d6-5127-4466-8c81-00e99dab2696-2025-02-13T170000.000Z
    reference_title: "DNAH7 / primary ciliary dyskinesia (Limited)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "DNAH7 | HGNC:18661 | primary ciliary dyskinesia | MONDO:0016575 | AR | Limited"
    explanation: ClinGen records autosomal recessive inheritance for DNAH7 and primary ciliary dyskinesia in general.
pathophysiology:
- name: Loss of DNAH7 Inner-Arm Dynein Heavy Chain
  description: >-
    Missense variants in conserved residues and truncating variants both
    reduce DNAH7 protein in patient sperm.
  biological_scale: MOLECULAR
  genes:
  - preferred_term: DNAH7
    term:
      id: hgnc:18661
      label: DNAH7
  molecular_functions:
  - preferred_term: minus-end-directed microtubule motor activity
    modifier: DECREASED
    term:
      id: GO:0008569
      label: minus-end-directed microtubule motor activity
  cellular_components:
  - preferred_term: Inner dynein arm
    term:
      id: GO:0036156
      label: inner dynein arm
  downstream:
  - target: Inner Dynein Arm Loss in the Sperm Flagellum
    causal_link_type: DIRECT
  - target: Inner Dynein Arm Loss in Respiratory Cilia
    causal_link_type: DIRECT
    description: >-
      Expected from DNAH7's location in respiratory inner arms; not
      demonstrated in a patient with known DNAH7 variants.
    evidence:
    - reference: PMID:39056782
      reference_title: "Primary Ciliary Dyskinesia Associated Disease-Causing Variants in CCDC39 and CCDC40 Cause Axonemal Absence of Inner Dynein Arm Heavy Chains DNAH1, DNAH6, and DNAH7."
      supports: SUPPORT
      directness: INDIRECT
      evidence_source: IN_VITRO
      snippet: "In healthy control subjects, DNAH7 is localized throughout the entire length of ciliary axonemes"
      explanation: DNAH7 is a structural component of human respiratory cilia.
  evidence:
  - reference: PMID:34476482
    reference_title: "Bi-allelic mutations in DNAH7 cause asthenozoospermia by impairing the integrality of axoneme structure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The expression of DNAH7 in the spermatozoa from the DNAH7-defective patients was significantly decreased"
    explanation: Reduced DNAH7 protein in patient sperm with missense variants.
  - reference: PMID:40810911
    reference_title: "Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "immunofluorescent staining revealed a marked reduction of DNAH7 and other IDA-associated proteins, such as DNAH3 and DNAH6, in the patients' spermatozoa"
    explanation: Loss of DNAH7 and of other inner-arm heavy chains in patient sperm with truncating variants.
- name: Inner Dynein Arm Loss in the Sperm Flagellum
  description: >-
    Transmission electron microscopy shows inner dynein arms missing from
    patient sperm flagella, while outer-arm proteins are kept. The
    remaining motors cannot drive normal flagellar beating.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: Sperm
    term:
      id: CL:0000019
      label: sperm
  cellular_components:
  - preferred_term: Sperm flagellum
    term:
      id: GO:0036126
      label: sperm flagellum
  biological_processes:
  - preferred_term: Inner dynein arm assembly
    modifier: DECREASED
    term:
      id: GO:0036159
      label: inner dynein arm assembly
  - preferred_term: Flagellated sperm motility
    modifier: DECREASED
    term:
      id: GO:0030317
      label: flagellated sperm motility
  downstream:
  - target: Absent inner dynein arms in sperm flagella
    causal_link_type: DIRECT
  - target: Multiple morphological abnormalities of the sperm flagella
    causal_link_type: DIRECT
  - target: Reduced sperm motility
    causal_link_type: DIRECT
  - target: Male infertility
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:34476482
    reference_title: "Bi-allelic mutations in DNAH7 cause asthenozoospermia by impairing the integrality of axoneme structure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The spermatozoa from the patients with DNAH7 bi-allelic mutations showed specific losses in the inner dynein arms."
    explanation: Inner-arm loss in sperm of men with missense variants.
  - reference: PMID:40810911
    reference_title: "Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "transmission electron microscopy results indicated a severe loss of inner dynein arms (IDAs) in the sperm flagella of both patients"
    explanation: Inner-arm loss in sperm of men with truncating variants.
  - reference: PMID:35543642
    reference_title: "Loss of function mutation in DNAH7 induces male infertility associated with abnormalities of the sperm flagella and mitochondria in human."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The axoneme structure of the sperm from a DNAH7-deficient patient revealed the loss of inner dynein arms."
    explanation: Inner-arm loss in the sperm of a third independent patient.
  - reference: PMID:40810911
    reference_title: "Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the expression of the outer dynein arms (ODA)-associated proteins, including DNAH8, DNAH11, DNAH17 and DNAI1, was comparable to that in normal controls"
    explanation: The defect is confined to the inner arms.
- name: Inner Dynein Arm Loss in Respiratory Cilia
  description: >-
    In one PCD patient whose respiratory cilia lacked inner dynein arms and
    moved abnormally, DNAH7 was made in the cell but missing from the cilia.
    That patient was not genotyped, so the lesion may have been in another
    gene. The only patient with biallelic DNAH7 variants whose airway cilia
    were examined, a man homozygous for a frameshift, had normal ciliary
    ultrastructure on electron microscopy. An inner-arm defect in airway
    cilia is therefore expected from DNAH7's location but has not been shown
    in a genotyped CILD50 patient.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: Respiratory tract multiciliated cell
    term:
      id: CL:4030034
      label: respiratory tract multiciliated cell
  cellular_components:
  - preferred_term: Inner dynein arm
    term:
      id: GO:0036156
      label: inner dynein arm
  biological_processes:
  - preferred_term: Cilium movement
    modifier: DECREASED
    term:
      id: GO:0003341
      label: cilium movement
  downstream:
  - target: Impaired Mucociliary Clearance
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:11877439
    reference_title: "Identification of dynein heavy chain 7 as an inner arm component of human cilia that is synthesized but not assembled in a case of primary ciliary dyskinesia."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: IN_VITRO
    snippet: "In cilia from PCD cells, DNAH7 was undetectable, whereas intracellular DNAH7 was clearly present."
    explanation: DNAH7 absent from the cilia of a PCD patient lacking inner arms; the patient's genotype was not determined.
  - reference: PMID:31443223
    reference_title: "Clinical and Genetic Analysis of Children with Kartagener Syndrome."
    supports: SUPPORT
    quote_role: BACKGROUND
    evidence_source: HUMAN_CLINICAL
    snippet: "It was found to be missing in a patient with PCD who had an absence of IDA and displayed abnormal cilia motility, but with normal ODA"
    explanation: Records that the 2002 patient's cilia moved abnormally as well as lacking inner arms.
  - reference: PMID:37998386
    reference_title: "Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype."
    supports: REFUTE
    evidence_source: IN_VITRO
    snippet: "In addition, we observed normal ciliary ultrastructure in patients with variants in the PCD candidate genes DNAH1 (n = 2) and DNAH7 (n = 1; Figure 4)."
    explanation: >-
      Electron microscopy of nasal brush biopsies from a man homozygous for a
      DNAH7 frameshift showed no inner-arm loss. It does not exclude a
      functional inner-arm defect, but it is the only direct look at airway
      cilia in a genotyped patient, and it found no structural defect.
- name: Impaired Mucociliary Clearance
  description: >-
    If respiratory inner arms fail, mucus clearance from the airways falls,
    as in other PCD forms, leading to chronic sinus and bronchial infection
    and bronchiectasis. Clearance has not been measured in a CILD50 patient,
    and the airway phenotypes below rest on very few patients, so this
    step is inferred from the general PCD mechanism.
  biological_scale: TISSUE
  biological_processes:
  - preferred_term: Mucociliary clearance
    modifier: DECREASED
    term:
      id: GO:0120197
      label: mucociliary clearance
  downstream:
  - target: Chronic sinusitis
    causal_link_type: DIRECT
  - target: Chronic bronchitis
    causal_link_type: DIRECT
  - target: Bronchiectasis
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Repeated airway infection and inflammation damage the bronchial wall.
  evidence:
  - reference: PMID:34476482
    reference_title: "Bi-allelic mutations in DNAH7 cause asthenozoospermia by impairing the integrality of axoneme structure."
    supports: SUPPORT
    quote_role: BACKGROUND
    directness: INDIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Dynein protein arms play a crucial role in the motility of both the cilia and flagella, and defects in these proteins generally impair the axoneme structure and cause primary ciliary dyskinesia."
    explanation: General statement that dynein arm defects cause PCD; not a finding in DNAH7 patients.
phenotypes:
- category: Reproductive
  name: Male infertility
  description: >-
    Primary male infertility is the presenting problem in the six men found
    through infertility screening. Fertility was not reported for the man
    found through a bronchiectasis clinic.
  phenotype_term:
    preferred_term: Male infertility
    term:
      id: HP:0003251
      label: Male infertility
  evidence:
  - reference: PMID:40810911
    reference_title: "Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "loss-of-function variants in DNAH7 were identified in two unrelated infertile men with asthenozoospermia"
    explanation: Male infertility in patients with truncating variants.
- category: Reproductive
  name: Reduced sperm motility
  description: >-
    Asthenozoospermia is the defining semen finding in the six men found
    through infertility screening.
  phenotype_term:
    preferred_term: Asthenozoospermia
    term:
      id: HP:0012207
      label: Reduced sperm motility
  evidence:
  - reference: PMID:34476482
    reference_title: "Bi-allelic mutations in DNAH7 cause asthenozoospermia by impairing the integrality of axoneme structure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "we recruited 85 infertile patients with idiopathic asthenozoospermia and identified bi-allelic mutations in DNAH7 (NM_018897.3) from three patients using whole-exome sequencing"
    explanation: Asthenozoospermia in men with missense variants.
- category: Reproductive
  name: Absent inner dynein arms in sperm flagella
  description: >-
    Seen in sperm flagella by electron microscopy. HP:0012257 Absent inner
    dynein arms is defined for respiratory motile cilia, so it is not used
    here; the airway cilia of the one genotyped patient examined were
    normal. HPO has no sperm-specific dynein arm term (OLS search of hp for
    "dynein arm" returns only respiratory cilia terms), so the finding is
    bound to the parent Abnormal sperm axoneme morphology.
  phenotype_term:
    preferred_term: Absent inner dynein arms in sperm flagella
    term:
      id: HP:0033524
      label: Abnormal sperm axoneme morphology
  evidence:
  - reference: PMID:40810911
    reference_title: "Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "transmission electron microscopy results indicated a severe loss of inner dynein arms (IDAs) in the sperm flagella of both patients"
    explanation: Ultrastructural inner-arm loss in patient sperm.
- category: Reproductive
  name: Multiple morphological abnormalities of the sperm flagella
  description: >-
    MMAF was reported in the patient with a loss-of-function variant
    described in 2022; the other reports describe asthenozoospermia without
    stating this. HPO has no MMAF term, so the finding is bound to Abnormal
    sperm tail morphology.
  phenotype_term:
    preferred_term: Multiple morphological abnormalities of the sperm flagella
    term:
      id: HP:0012868
      label: Abnormal sperm tail morphology
  evidence:
  - reference: PMID:35543642
    reference_title: "Loss of function mutation in DNAH7 induces male infertility associated with abnormalities of the sperm flagella and mitochondria in human."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "we showed that DNAH7 disruption in humans results in male infertility, which was characterised by multiple morphological abnormalities of sperm flagella"
    explanation: MMAF in a man with DNAH7 disruption.
- category: Respiratory
  name: Chronic sinusitis
  description: >-
    Listed by ClinGen among the common phenotypes of CILD50. The one patient
    with tabulated clinical detail had chronic rhinosinusitis with nasal
    polyps (CRSwNP).
  phenotype_term:
    preferred_term: Chronic sinusitis
    term:
      id: HP:0011109
      label: Chronic sinusitis
  evidence:
  - reference: CGGV:assertion_90a097d6-5127-4466-8c81-00e99dab2696-2025-02-13T170000.000Z
    reference_title: "DNAH7 / primary ciliary dyskinesia (Limited)"
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: "Some of the most common patient phenotypes are: Absent inner dynein arms, Chronic sinusitis and Chronic bronchitis."
    explanation: ClinGen's evidence summary for DNAH7 and PCD50 names chronic sinusitis as a common patient phenotype.
  - reference: PMID:37998386
    reference_title: "Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Early onset of chronic wet cough and CRSwNP, parental consanguinity, and P. aeruginosa infection | DNAH7 | c.12056_12060delTATGT c.12056_12060delTATGT | p.(Leu4019Serfs*3)"
    explanation: >-
      Table 1 row for the patient homozygous for a DNAH7 frameshift. CRSwNP
      is defined in the table footnote as chronic rhinosinusitis with nasal
      polyps.
- category: Respiratory
  name: Chronic bronchitis
  description: >-
    Listed by ClinGen, and in the OMIM definition, as a feature of CILD50.
    The underlying patient-level reports could not be quoted (see notes).
  phenotype_term:
    preferred_term: Chronic bronchitis
    term:
      id: HP:0004469
      label: Chronic bronchitis
  evidence:
  - reference: CGGV:assertion_90a097d6-5127-4466-8c81-00e99dab2696-2025-02-13T170000.000Z
    reference_title: "DNAH7 / primary ciliary dyskinesia (Limited)"
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: "Some of the most common patient phenotypes are: Absent inner dynein arms, Chronic sinusitis and Chronic bronchitis."
    explanation: ClinGen's evidence summary for DNAH7 and PCD50 names chronic bronchitis as a common patient phenotype.
- category: Respiratory
  name: Bronchiectasis
  description: >-
    Computed tomography-confirmed bronchiectasis in the patient homozygous
    for a DNAH7 frameshift, with chronic wet cough, Pseudomonas aeruginosa
    infection and a percent-predicted FEV1 of 32. One patient only.
  phenotype_term:
    preferred_term: Bronchiectasis
    term:
      id: HP:0002110
      label: Bronchiectasis
  evidence:
  - reference: PMID:37998386
    reference_title: "Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "At inclusion in our study, all patients had bronchiectasis without a definite diagnosis of PCD."
    explanation: The cohort, which included the DNAH7 patient, was selected for bronchiectasis.
  - reference: PMID:37998386
    reference_title: "Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Early onset of chronic wet cough and CRSwNP, parental consanguinity, and P. aeruginosa infection | DNAH7 | c.12056_12060delTATGT c.12056_12060delTATGT | p.(Leu4019Serfs*3)"
    explanation: Identifies the DNAH7 patient within the bronchiectasis cohort and his airway history.
genetic:
- name: DNAH7
  association: Causal
  gene_term:
    preferred_term: DNAH7
    term:
      id: hgnc:18661
      label: DNAH7
  notes: >-
    Reported genotypes: biallelic missense variants in three of 85 Chinese
    men with asthenozoospermia (PMID:34476482), and compound heterozygous
    truncating variants in two men, c.9702_9705del (p.Phe3234Leufs*52) with
    c.768G>A (p.Trp256*), and c.5650C>T (p.Arg1884*) with c.768G>A
    (PMID:40810911). A further infertile man with a loss-of-function variant
    and MMAF was reported in 2022 (PMID:35543642). A 51-year-old Turkish man
    with bronchiectasis and possible PCD was homozygous for
    c.12056_12060delTATGT (p.Leu4019Serfs*3), classed as a variant of
    uncertain significance because DNAH7 is a candidate gene; his airway
    cilia were ultrastructurally normal (PMID:37998386). The shared p.Trp256* allele in two unrelated men may be
    recurrent. A Portuguese child with Kartagener syndrome carried two DNAH7
    missense variants together with two truncating DNAH5 variants
    (PMID:31443223); the authors consider DNAH5 the main cause, so this case
    does not establish DNAH7 as a respiratory PCD gene.
  evidence:
  - reference: PMID:34476482
    reference_title: "Bi-allelic mutations in DNAH7 cause asthenozoospermia by impairing the integrality of axoneme structure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our study is the first to demonstrate that bi-allelic mutations in DNAH7 may impair the integrality of axoneme structure, affect sperm motility, and cause asthenozoospermia in humans."
    explanation: First human genetic report for DNAH7.
  - reference: PMID:40810911
    reference_title: "Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "our findings confirmed that DNAH7 variants may contribute to asthenozoospermia by affecting flagellar IDA assembly"
    explanation: Independent replication with truncating alleles.
  - reference: PMID:35543642
    reference_title: "Loss of function mutation in DNAH7 induces male infertility associated with abnormalities of the sperm flagella and mitochondria in human."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Thus, DNAH7 is critical for axoneme and mitochondrial development in human sperm."
    explanation: A third report of DNAH7 loss of function in an infertile man.
  - reference: PMID:37998386
    reference_title: "Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Early onset of chronic wet cough and CRSwNP, parental consanguinity, and P. aeruginosa infection | DNAH7 | c.12056_12060delTATGT c.12056_12060delTATGT | p.(Leu4019Serfs*3)"
    explanation: >-
      Homozygous DNAH7 frameshift in an adult with bronchiectasis and chronic
      upper and lower airway disease. The authors classed him as possible
      PCD; his nasal nitric oxide was not low and his ciliary ultrastructure
      was normal, so the case supports a respiratory phenotype only weakly.
  - reference: PMID:31443223
    reference_title: "Clinical and Genetic Analysis of Children with Kartagener Syndrome."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "The variants in gene DNAH5 are potentially more damaging and are, thus, expected to be the major factor responsible for Patient-2 phenotype. Nevertheless, DNAH7 may have an accumulative effect, leading to the complete loss of both DAs."
    explanation: >-
      The only Kartagener patient with DNAH7 variants also had DNAH5
      variants the authors judged more damaging, so the case is weak support
      for a respiratory DNAH7 phenotype. The authors still propose an
      additive DNAH7 contribution.
  - reference: CGGV:assertion_90a097d6-5127-4466-8c81-00e99dab2696-2025-02-13T170000.000Z
    reference_title: "DNAH7 / primary ciliary dyskinesia (Limited)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "DNAH7 | HGNC:18661 | primary ciliary dyskinesia | MONDO:0016575 | AR | Limited"
    explanation: >-
      ClinGen rates DNAH7 as Limited for primary ciliary dyskinesia in
      general. The assertion is for MONDO:0016575, not this numbered entity,
      so it is quoted here rather than recorded as gene_disease_validity.
diagnosis:
- name: Exome Sequencing in Asthenozoospermia
  description: >-
    All reported patients were found by exome sequencing of infertile men
    with asthenozoospermia, supported by sperm electron microscopy showing
    inner-arm loss and immunostaining showing missing DNAH7.
  diagnosis_term:
    preferred_term: Whole exome sequencing
    term:
      id: NCIT:C101295
      label: Whole Exome Sequencing
  evidence:
  - reference: PMID:34476482
    reference_title: "Bi-allelic mutations in DNAH7 cause asthenozoospermia by impairing the integrality of axoneme structure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "identified bi-allelic mutations in DNAH7 (NM_018897.3) from three patients using whole-exome sequencing"
    explanation: Diagnostic route in the founding report.
differential_diagnoses:
- name: Primary ciliary dyskinesia 14 (CCDC39-related axonemal ruler defect)
  disease_term:
    preferred_term: primary ciliary dyskinesia 14
    term:
      id: MONDO:0013434
      label: primary ciliary dyskinesia 14
  description: >-
    Axonemal ruler defects caused by CCDC39 or CCDC40 also remove DNAH7 from
    respiratory cilia, so absent DNAH7 staining in a ciliary biopsy does not
    by itself point to DNAH7.
  distinguishing_features:
  - >-
    CCDC39/40 disease causes axonemal disorganization and loss of several
    inner-arm heavy chains (DNAH1, DNAH6, DNAH7) together with typical PCD
    airway disease. In CILD50 inner-arm loss has been shown only in sperm,
    and the one examined airway sample had normal ultrastructure.
  evidence:
  - reference: PMID:39056782
    reference_title: "Primary Ciliary Dyskinesia Associated Disease-Causing Variants in CCDC39 and CCDC40 Cause Axonemal Absence of Inner Dynein Arm Heavy Chains DNAH1, DNAH6, and DNAH7."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "demonstrated that the IDA heavy chains DNAH1, DNAH6, and DNAH7 are conspicuously absent within the respiratory ciliary axonemes by immunofluorescence analyses"
    explanation: Secondary DNAH7 loss in CCDC39/40 PCD.
treatments:
- name: Intracytoplasmic Sperm Injection
  description: >-
    ICSI bypasses the motility defect. Patients in all three sperm genetic reports
    fathered children or achieved pregnancies through ICSI.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: Intracytoplasmic Sperm Injection
    term:
      id: NCIT:C185482
      label: Intracytoplasmic Sperm Injection
  target_mechanisms:
  - target: Inner Dynein Arm Loss in the Sperm Flagellum
    description: Direct injection makes flagellar motility irrelevant to fertilization.
    evidence:
    - reference: PMID:40810911
      reference_title: "Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "the infertility of the patients harboring DNAH7 mutations could be successfully overcome by intracytoplasmic sperm injection treatment"
      explanation: ICSI success in patients with truncating variants.
  evidence:
  - reference: PMID:34476482
    reference_title: "Bi-allelic mutations in DNAH7 cause asthenozoospermia by impairing the integrality of axoneme structure."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "these patients were able to have their children via intra-cytoplasmic sperm injection treatment"
    explanation: ICSI success in patients with missense variants.
  - reference: PMID:35543642
    reference_title: "Loss of function mutation in DNAH7 induces male infertility associated with abnormalities of the sperm flagella and mitochondria in human."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Live birth was achieved via intracytoplasmic sperm injection."
    explanation: ICSI success in the patient with MMAF.
- name: Airway Clearance and Chronic Infection Management
  description: >-
    There is no treatment for the ciliary defect. Patients with airway
    disease receive the supportive care used across primary ciliary
    dyskinesia: airway clearance, prompt treatment of infections, and
    surveillance of lung function. Nothing in it is DNAH7-specific.
  therapeutic_modality: OTHER
  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 mucus
      transport the cilia cannot provide, and antibiotics treat the
      infections that follow. Neither restores ciliary function.
  evidence:
  - reference: PMID:38891105
    reference_title: "Primary Ciliary Dyskinesia: A Clinical Review."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: HUMAN_CLINICAL
    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: >-
      Review statement of standard PCD airway management. It covers PCD in
      general and is not specific to DNAH7.

📚

References & Deep Research

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 50 (DNAH7) · 2026-10-14T20:20:49Z · View source

New entry for CILD50 (MONDO:0957252), the DNAH7-related disorder, also listed as a has_subtypes row on the umbrella Primary_Ciliary_Dyskinesia entry (not edited). Deep research: the requested falcon provider failed authentication (503) on two attempts, including with --fallback, so the report used is research/Primary_Ciliary_Dyskinesia_50-deep-research-claude_code.md; just preflight-dr against MONDO:0957252 returned PASS. The human genetic evidence is two Chinese asthenozoospermia studies (PMID:34476482 missense, PMID:40810911 truncating; both abstract-only) showing inner dynein arm loss in sperm and ICSI success. No genotyped DNAH7 patient has documented airway disease or ciliary studies, so no respiratory phenotypes were recorded; the respiratory branch (PMID:11877439, a 2002 ungenotyped PCD case lacking ciliary DNAH7, and PMID:39056782) is marked hypothetical and ends at mucociliary clearance without phenotype edges. A Kartagener child with DNAH7 plus DNAH5 variants (PMID:31443223) is recorded as weak, confounded support. No animal model was curated. ClinGen rates DNAH7 Limited for generic PCD (MONDO:0016575), so no gene_disease_validity was recorded. Validated with just validate, count-verified-snippets (all verified), validate-terms, check-entity-refs, check-causal-targets, check-duplicate-keys and validate-disorders.

Claude Code ▸

Research Report: Primary Ciliary Dyskinesia 50 (CILD50, DNAH7-related)

claude-haiku-5-5, claude-sonnet-5-5 5 citations 2026-10-14T20:09:21.488635

Checking the 2025 DNAH7 paper next, then I'll write the report.

Research Report: Primary Ciliary Dyskinesia 50 (CILD50, DNAH7-related)

Evidence caveat. This report rests on only a few sources I could open: the ZFIN/Disease Ontology entry for OMIM:620356, a fetched page for the 2021 Acta Biochim Biophys Sin paper, a PubMed search listing, and an Ensembl lookup. OMIM and PubMed abstracts returned 403 or cookie pages, so I have no verbatim abstract for any paper. Two quotes below come from a summary of the 2021 paper's abstract and are marked as such. Everything that is general knowledge about PCD, not DNAH7-specific, is labelled "inferred" or "not verified". Nothing here is ready to use as a snippet without just fetch-reference and checking against the cached text.

1. Disease information

Name and identifiers. Ciliary dyskinesia, primary, 50 (CILD50; PCD50). OMIM phenotype #620356, gene OMIM 610061. The ZFIN/DO entry gives the MONDO ID MONDO:0957252 as supplied in the request. I could not independently confirm that ID, and a MONDO search returned no hit for it. Look it up in OLS before binding it.
Overview. The Disease Ontology definition describes a form of PCD caused by homozygous or compound heterozygous mutation in DNAH7 (2q32). It lists chronic sinusitis, bronchitis and male infertility, with sperm flagella defects tied to loss of inner dynein arms (IDAs) (ZFIN DOID:0070763).
Synonym. CILD50.
Data origin. The case-level data come from small research cohorts of infertile men, not EHR. The disease-level definition is aggregated from OMIM and DO.

2. Etiology

Cause. Biallelic (recessive) DNAH7 variants. DNAH7 encodes an axonemal inner-arm dynein heavy chain.
Risk and protective factors, gene-environment interactions. None reported for this entity in the sources I saw.

3. Phenotypes (HPO suggestions are inferred, not looked up)

Evidence is limited to three men in the 2021 study and an apparent 2025 follow-up.

Phenotype	Suggested HPO (verify)	Notes
Asthenozoospermia	HP:0012206	Motility reduced, other semen parameters mostly normal (2021 paper)
Male infertility	HP:0003251	Primary infertility; all three couples conceived by ICSI
Chronic sinusitis	HP:0011109	"PCD-like symptoms, including chronic sinusitis and bronchitis" (from a summary of the 2021 abstract)
Chronic bronchitis	HP:0004469	As above

Not established. The sources I saw do not establish situs inversus, neonatal respiratory distress, bronchiectasis or otitis media for this subtype. I could not check frequency, onset or quality of life.
Caution. The 2021 paper describes the men as having normal physical development, hormones, genitalia and testes. The respiratory phenotype comes from only three patients.

4. Genetic and molecular information

Gene. DNAH7 (hgnc ID not looked up; resolve it with just validate-terms). It is at chr2:195,737,524–196,068,848 (GRCh38), reverse strand. The Ensembl ID is ENSG00000118997, with canonical transcript ENST00000312428.11.
Variants. The 2021 paper (NM_018897.3) reported:

Patient	Variant	Protein change
P1 (homozygous)	c.10390G>A	p.G3464S
P2	c.5587G>A	p.D1863N
P2	c.6492G>A	p.M2164I
P3	c.9611G>A	p.R3204H
P3	c.10601A>G	p.Q3534R

All are missense variants in AAA domains and were predicted damaging. c.10390G>A and c.10601A>G were novel in gnomAD. The "loss-of-function" label for the 2025 paper's title is from the search listing only. - Origin. Germline. - Modifier genes, epigenetics, chromosomal abnormalities. None identified.

5. Environmental information

None identified in the sources reviewed.

6. Mechanism and pathophysiology

Causal chain (steps 3 to 5 are demonstrated in patient sperm; steps 6 and 7 are inferred from the general PCD model):

Biallelic germline DNAH7 variants alter conserved AAA-domain residues.
This is expected to impair DNAH7 inner-arm dynein heavy chain function (inferred).
DNAH7 signal along patient sperm flagella is decreased.
DNAH1, another IDA marker, is also reduced.
Transmission electron microscopy shows severe IDA loss. The outer dynein arm marker DNAI2, the radial spoke marker RSPH1 and the periaxonemal marker AKAP4 stain like controls.
Loss of IDAs weakens axonemal motility, which gives asthenozoospermia and male infertility.
By analogy, impaired motile cilia would cause chronic sinus and bronchial disease (inferred; direct ciliary data are not in the sources I read).
Suggested GO terms (unverified): inner dynein arm (GO:0036156), axonemal dynein complex assembly (GO:0070286), cilium movement (GO:0003341). Pull the exact CURIEs and labels from OLS or the term cache.
Cell types: spermatozoon (CL:0000019) and respiratory ciliated epithelial cell (CL:0002145). Verify both.
Omics and advanced technologies. I found none.

7. Anatomical structures affected

Sperm flagellum axoneme: directly shown.
Upper and lower respiratory tract: chronic sinusitis and bronchitis reported.
UBERON and lateralization: not verified.

8–9. Temporal development, inheritance and population

Inheritance. Autosomal recessive, with both homozygous and compound heterozygous cases (HP:0000007; verify).
Prevalence, penetrance, founder effects, sex ratio. Not available. The PCD-wide prevalence estimate of roughly 1:7,500–1:20,000 from search results is not specific to this subtype.
Onset. Not reported. The affected men were identified in adulthood through infertility work-ups.

10. Diagnostics

Cohort screen. Whole-exome sequencing of 85 infertile men with idiopathic asthenozoospermia found biallelic DNAH7 variants in three.
Sperm TEM. Showed IDA loss.
Sperm immunofluorescence. Showed reduced DNAH7 and DNAH1.
Not verified. Nasal nitric oxide, high-speed video analysis and nasal brush TEM in these patients. Standard PCD guidelines would apply, but none of the sources I read covers them.

11. Prognosis

No data.

12. Treatment

Reproductive. All three couples in the 2021 study had clinical pregnancies after intracytoplasmic sperm injection (ICSI). OMIM also notes successful ICSI pregnancy. A suggested NCIT term is a reproductive technique term; look it up.
Respiratory. Standard PCD supportive care (airway clearance, antibiotics for infections) is inferred and has no DNAH7-specific evidence in what I read.
Trials. None identified.

13. Prevention

Genetic counseling for an autosomal recessive condition. The ICSI outcome carries a recurrence-risk implication for offspring; carrier testing of partners is the usual approach, but I have no source on it.

14–15. Other species and model organisms

Not researched. The Tbc1d21 mouse paper (PMID 32976492) names Dnah7 as a candidate interactor of TBC1D21. That is not a Dnah7 model. A DNAH7 knockout phenotype should be checked at MGI and ZFIN.

Key references

PMID	Paper	Notes
34476482	Bi-allelic mutations in DNAH7 cause asthenozoospermia by impairing the integrality of axoneme structure. Acta Biochim Biophys Sin 53(10):1300–1309, 2021	Main source: OUP
40810911	Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans (2025)	Title only; read this next
32976492	Tbc1d21 deficiency causes male infertility (2020)	Peripheral

Next steps

Run just fetch-reference PMID:34476482 and PMID:40810911.
Read the OMIM #620356 text to see which paper it cites for the DNAH7 association. I could not tell whether the OMIM entry rests on the 2021 paper.
Check whether any DNAH7 case reports describe respiratory cilia directly. The respiratory phenotype for this entry currently rests on a few men's self-reported "PCD-like symptoms".
Per the lump/split rules in CLAUDE.md, decide whether this belongs as its own entry or a has_subtypes row on a PCD parent. The evidence base is thin.

Sources: - ZFIN DOID:0070763 (CILD50 definition) - Bi-allelic mutations in DNAH7 cause asthenozoospermia (OUP) - PubMed search listing for DNAH7 / asthenozoospermia - Ensembl DNAH7 lookup - OMIM #620356 (search listing only; page not opened)

Reference Validation

Checked with linkml-reference-validator 0.3.0.

Outcome	Count
References checked	3
Resolved	3
Unresolved (possible confabulation)	0
Unverifiable	0
References weighed for topical relevance	3
On topic	3
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	13
Resolved	12
Unresolved (possible confabulation)	0
Obsolete	0
Unverifiable	1
Terms whose name was checked	6
Terms named correctly	3
Terms named as a different term	1
Terms whose name is worth a second look	2

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:

HP:0012206 (1 mention) - the report calls it "Asthenozoospermia"; HP calls it Abnormal sperm motility

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

DOID:0070763 (5 mentions) - the report calls it "CILD50 definition"; DOID calls it primary ciliary dyskinesia 50, and lists "CILD50" among its other names
CL:0000019 (1 mention) - the report calls it "Cell types: spermatozoon"; CL calls it sperm**, and lists "spermatozoon" among its other names

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: OMIM.

Primary Ciliary Dyskinesia 50

Ask OpenScientist

OpenScientist Report

Inheritance

Pathophysiology

Pathograph

Phenotypes

Genetic Associations

Medical Actions

Diagnosis

Differential Diagnoses

Source YAML

References & Deep Research

Deep Research

Research Report: Primary Ciliary Dyskinesia 50 (CILD50, DNAH7-related)

1. Disease information

2. Etiology

3. Phenotypes (HPO suggestions are inferred, not looked up)

4. Genetic and molecular information

5. Environmental information

6. Mechanism and pathophysiology

7. Anatomical structures affected

8–9. Temporal development, inheritance and population

10. Diagnostics

11. Prognosis

12. Treatment

13. Prevention

14–15. Other species and model organisms

Key references

Next steps

Reference Validation

Term Validation

Terms the report names something else

Terms whose name is worth a second look

Prefixes with no resolver