Cone-rod Dystrophy And Hearing Loss

Key Findings

1. CEP78 biallelic loss-of-function causes CRDHL, distinct from Usher syndrome (F001)

The founding evidence for CRDHL as a CEP78-related disorder comes from Namburi et al. 2016 (American Journal of Human Genetics). Using homozygosity mapping followed by whole-exome sequencing and founder-mutation screening, they identified two truncating variants in CEP78 — c.893-1G>A (a splice-acceptor variant) and c.534delT — in six individuals of Jewish ancestry with autosomal recessive cone-rod degeneration and SNHL. The c.893-1G>A variant causes skipping of exon 7 (a 65-bp deletion), producing a frameshift p.Asp298Valfs*17. Crucially, immunohistochemistry of human retina showed intense CEP78 labeling of cone inner segments relative to rods, providing an anatomical basis for the cone-predominant degeneration.

"Homozygosity mapping followed by whole-exome sequencing (WES) and founder mutation screening revealed two truncating rare variants (c.893-1G>A and c.534delT) in CEP78, which encodes centrosomal protein 78, in six individuals of Jewish ancestry with CRD and SNHL." — PMID: 27588452

This finding establishes CEP78 truncating variants as the cause of a new, non-Usher deaf-blindness syndrome, distinguished by its cone-first (rather than rod-first) retinal degeneration and post-lingual (rather than congenital) hearing loss.

2. CEP78 is a centriolar distal-end protein controlling centriole length and centrosome homeostasis (F002)

The molecular function of CEP78 places CRDHL firmly among the ciliopathies. Hossain et al. 2017 (Journal of Cell Biology) showed that CEP78 localizes to mature centrioles, directly interacts with VprBP (viral protein R binding protein), and inhibits the EDD-DYRK2-DDB1 E3 ubiquitin ligase to regulate centrosome homeostasis.

"Here, we show that centrosomal protein of 78 kDa (Cep78) localizes to mature centrioles and directly interacts with viral protein R binding protein (VprBP)." — PMID: 28242748

Karasu et al. 2022 further demonstrated that the CEP350-FOP scaffold recruits CEP78 (or OFD1) to the distal end of centrioles, and that the CEP350-FOP/CEP78 complex controls centriole microtubule length:

"recruiting the proteins CEP78 and OFD1 to the distal end of centrioles and promoting the assembly of subdistal appendages" — PMID: 36315013

Consistent with this, Ascari et al. 2020 found that patient-derived fibroblasts and nasal brushings show elongated primary cilia, indicating impaired cilia assembly downstream of CEP78 loss:

"Elongated primary cilia without clear ultrastructural abnormalities in sperm or nasal brushes suggest impaired cilia assembly." — PMID: 31999394

3. The phenotype spectrum includes male infertility; a missense founder allele expands variant type (F003)

Ascari et al. 2020 identified and functionally characterized the first CEP78 missense variant, c.449T>C p.(Leu150Ser), across three CRDHL families (biallelic in two Belgian families; compound heterozygous with c.1462-1G>T in a German family). Haplotype analysis demonstrated a founder effect, and homology modeling plus patient fibroblasts confirmed reduced protein stability. Two affected males had sperm abnormalities causing infertility, expanding the phenotype.

"we identified and functionally characterized the first CEP78 missense variant c.449T>C, p.(Leu150Ser) in three CRDHL families" — PMID: 31999394

"the CEP78 phenotype has been possibly expanded with male infertility" — PMID: 31999394

This finding shows that CRDHL is not confined to null alleles — destabilizing missense variants also cause disease — and that the syndrome extends beyond the eye and ear to the male reproductive tract.

4. CEP250 (C-Nap1) is a second CRDHL/atypical-Usher locus (F004)

Kubota et al. 2018 reported compound heterozygous null variants c.361C>T p.R121* and c.562C>T p.R188* in CEP250, co-segregating with mild cone-rod dystrophy and slight SNHL in a Japanese family (both variants PVS1, pathogenic by ACMG). C-Nap1/CEP250 is expressed in photoreceptor cilia and interacts with other ciliary proteins, including CEP78.

"Our data indicate that mutations of CEP250 can cause mild CRD and SNHL in Japanese patients." — PMID: 29718797

"Mutations of CEP250 cause atypical Usher syndrome which is characterized by early-onset sensorineural hearing loss (SNHL) and a relatively mild retinitis pigmentosa." — PMID: 29718797

CEP250 thus represents locus heterogeneity within the CRDHL phenotype and reinforces the centriolar-cilium theme, since CEP250 and CEP78 are physically and functionally interconnected at the centrosome.

5. No disease-specific therapy exists; cochlear implantation restores speech perception (F005)

There is no approved gene or pharmacologic therapy for CEP78- or CEP250-related CRDHL. Management is symptomatic and rehabilitative — low-vision aids, hearing aids, cochlear implantation, and genetic counseling. The strongest quantitative evidence for the SNHL component comes from the analogous post-lingual syndrome Usher type IIa: Hartel et al. 2017 implanted 8 USH2a adults (mean age 59 at implantation) and found phoneme scores improved from 41% to 87% (p = 0.02), with clear quality-of-life benefit.

"The phoneme scores improved significantly from 41 to 87% in patients with USH2a (p = 0.02)" — PMID: 28498263

"CI increases speech intelligibility and improves quality of life in patients with USH2a." — PMID: 28498263

Because CRDHL hearing loss is likewise bilateral, post-lingual, and progressive, cochlear implantation is expected to provide comparable benefit — particularly important given the concurrent progressive visual loss that increases reliance on hearing.

6. CRDHL is one of several retinal-dystrophy-plus-hearing-loss syndromes requiring differential diagnosis (F006)

CRDHL must be distinguished from other dual sensory-loss disorders:

"This subtype was assigned as 'USH IV' with a late onset of RP and usually late-onset progressive SNHL without vestibular involvement." — PMID: 39199020

"PHARC syndrome is an autosomal recessive neurodegenerative disease caused by mutations in the ABHD12 gene and is characterized by five main clinical features: polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataracts." — PMID: 40064796

"we identified two heterozygous mutations affecting Arg391 in β-tubulin 4B isotype-encoding (TUBB4B)" — PMID: 29198720

7. Retinal component: childhood-onset, cone-first, progressive dystrophy → legal blindness by mid-adulthood; hearing loss variably expressed (F007)

The retinal disease of CRDHL follows the natural history of cone-rod dystrophy defined in the 19-year multicenter cohort of Thiadens et al. 2012: CRD had a mean age of onset of 12 years (SD 11), was AR in 90%, and reached legal blindness at a mean age of 35 years (SE 1.1) — significantly earlier than cone-only dystrophy (48 years, P<0.001). Ten years after diagnosis, 51% had bull's-eye maculopathy and 70% had absolute peripheral field defects.

"The mean age of legal blindness was 48 (standard error [SE], 3.1) years in CD, and 35 (SE, 1.1; P<0.001) years in CRD." — PMID: 22264887

"The mean age onset for CD was 16 years (standard deviation, 11), and of CRD 12 years (standard deviation, 11; P = 0.02)." — PMID: 22264887

The hearing-loss component shows variable expressivity and onset. Zhai & Ballios 2024 documented teenage CEP78 siblings with cone-rod dystrophy and "presumed normal hearing" alongside another patient with "cone-rod dystrophy and early-onset hearing loss":

"Both teenagers have a clinical diagnosis of cone-rod dystrophy with presumed normal hearing." — PMID: 38780195

8. Diagnosis relies on multimodal ophthalmic + audiologic phenotyping plus panel/exome sequencing (F008)

Diagnosis integrates: - Full-field electroretinography — cone-rod pattern (photopic responses reduced earlier/more than scotopic) - Multimodal retinal imaging — OCT (outer-retinal/ellipsoid-zone and photoreceptor loss), fundus autofluorescence, adaptive optics (reduced cone density) - Pure-tone audiometry — bilateral SNHL - Molecular confirmation — retinal-dystrophy gene panels or whole-exome/whole-genome sequencing

de Castro-Miró et al. 2016 identified CEP78 and CEP250 as new inherited-retinal-dystrophy (IRD) genes via WES:

"WES unveiled four new candidates for non-syndromic IRD: SEMA6B, CEP78, CEP250, SCLT1, the two latter previously associated to syndromic disorders." — PMID: 28005958

"We provide functional data supporting that missense mutations in CEP250 alter cilia formation." — PMID: 28005958

Zhai & Ballios 2024 showed that retinal-dystrophy panels detect variants (including a splice variant c.1206-2A>C, and a nonsense c.1447C>T p.Arg483*) that earlier WES had missed:

"A retinal dystrophy panel detected a novel homozygous CEP78 pathogenic variant (c.1447C>T, p.Arg483*)" — PMID: 38780195

9. An ultra-rare AR disorder with population-specific CEP78 founder alleles and a role for consanguinity (F009)

CRDHL is autosomal recessive and ultra-rare — only several dozen molecularly confirmed cases have been reported worldwide across CEP78 and CEP250. Founder effects are documented: the CEP78 truncating variants c.893-1G>A and c.534delT recurred in Jewish-ancestry individuals identified through homozygosity mapping (consistent with consanguinity/shared haplotypes), and the missense c.449T>C p.(Leu150Ser) allele is a founder allele across Belgian and German families.

"Homozygosity mapping followed by whole-exome sequencing (WES) and founder mutation screening revealed two truncating rare variants (c.893-1G>A and c.534delT) in CEP78" — PMID: 27588452

"Haplotype reconstruction showed a founder effect." — PMID: 31999394

Both sexes are affected for the retinal/auditory phenotype; reduced fertility affects males specifically. CEP250 variants were reported in a non-consanguineous Japanese family.

10. Anatomical targets: cone-predominant photoreceptors, cochlear hair cells, and sperm flagella — a shared centriole/cilium defect (F010)

The primary organs affected are the eye (retina) and inner ear (cochlea), plus the male reproductive tract (testis/sperm). CEP78 is enriched in cone inner segments relative to rods, explaining the cone-predominant degeneration; CEP250/C-Nap1 localizes to photoreceptor cilia. The unifying subcellular lesion is at the centriole/basal body and ciliary axoneme — the photoreceptor connecting cilium, cochlear hair-cell kinocilium/basal body, and sperm flagellar axoneme all depend on centriolar/ciliary integrity.

"Immunohistochemistry studies in the human retina showed intense labeling of cone inner segments compared to rods." — PMID: 27588452

"C-Nap1 has been reported to be expressed in the photoreceptor cilia" — PMID: 29718797

11. Model systems: Cep78-knockout mouse and patient-derived ciliated cells (F011)

• Mammalian model: The Cep78-knockout mouse (Mus musculus; NCBI Taxon:10090) recapitulates the male-infertility component. Liu et al. 2025: "Cep78 knockout causes sterility and oligoasthenoteratozoospermia in male mice." — PMID: 39747485
• Patient-derived in vitro models: Dermal fibroblasts and nasal-epithelial brushings from patients show elongated primary cilia and reduced CEP78 protein stability (PMID: 31999394).
• Cell-biology models: HeLa/RPE cultured cells established CEP78's centriolar localization, VprBP interaction, and EDD-DYRK2-DDB1 inhibition (PMID: 28242748), and CEP350-FOP-dependent recruitment controlling centriole length (PMID: 36315013).
• Differential-diagnosis models: ARSG has naturally occurring canine and murine neuronal ceroid lipofuscinosis models: "we identified a homozygous missense variant, p.(Arg99His), previously described in dogs with neuronal ceroid lipofuscinosis" — PMID: 39199020.

12. Consolidated pathophysiology causal chain (F012)

See the Mechanistic Model section below for the integrated causal chain.

Detailed Section-by-Section Report

Section 1 — Disease Information

CRDHL is a rare autosomal recessive syndrome combining a progressive cone-rod retinal dystrophy with sensorineural hearing loss, and (in males) reduced fertility. Key identifiers: MONDO:0014980; OMIM #617236 ("Cone-rod dystrophy and hearing loss 1," CRDHL1, CEP78); OMIM #618358 ("Cone-rod dystrophy and hearing loss 2," CRDHL2, CEP250); it lacks a dedicated ICD-10 code (coded under H35.5 hereditary retinal dystrophy plus H90.x sensorineural hearing loss). Synonyms: cone-rod dystrophy with sensorineural hearing loss; CRD-HL; CRDHL; CEP78-related deaf-blindness. Information is derived from aggregated disease-level resources (OMIM, published case series/cohorts) rather than EHR.

Section 2 — Etiology

Causal factors are purely genetic (monogenic, autosomal recessive): biallelic CEP78 loss-of-function/destabilizing variants (primary) or biallelic CEP250 null variants (second locus). Genetic risk factors: the disease requires two pathogenic alleles; documented founder alleles increase risk in specific ancestries. Environmental risk/protective factors and gene-environment interactions: not applicable — no environmental, infectious, lifestyle, or protective-allele factors have been reported for this Mendelian disorder.

Section 3 — Phenotypes

Quality-of-life impact: dual sensory loss severely affects communication, mobility, education, and employment; cochlear implantation and low-vision rehabilitation substantially mitigate the hearing component.

Section 4 — Genetic/Molecular Information

Causal genes: CEP78 (HGNC:26820; OMIM 617110), CEP250 (OMIM 611485). Variant types: truncating (splice c.893-1G>A → p.Asp298Valfs17; frameshift c.534delT; nonsense c.1447C>T p.Arg483), missense (c.449T>C p.Leu150Ser — destabilizing founder allele), and splice (c.1462-1G>T, c.1206-2A>C). Classification: pathogenic/likely pathogenic per ACMG (PVS1 for null alleles). Origin: germline. Functional consequence: loss of function (reduced/absent protein or protein stability). Allele frequencies: rare in gnomAD (consistent with ultra-rare recessive disease). Modifier/epigenetic/chromosomal factors: none established.

Section 5 — Environmental Information

Not applicable. No environmental toxins, radiation, lifestyle factors, or infectious agents contribute to this monogenic disorder.

Section 6 — Mechanism / Pathophysiology

Presented as an ordered causal chain in the Mechanistic Model section below.

Section 7 — Anatomical Structures Affected

Organ level: eye/retina (UBERON:0000966), inner ear/cochlea (UBERON:0001844), testis (UBERON:0000473). Body systems: visual, auditory, reproductive. Cell level: retinal cone cells (CL:0000573, primary), retinal rod cells (CL:0000604), cochlear/inner-ear hair cells (CL:0000855), spermatozoa/male germ cells (CL:0000019). Subcellular: centriole (GO:0005814), ciliary basal body (GO:0036064), photoreceptor connecting cilium (GO:0032391), sperm flagellum. Lateralization: bilateral (both retina and cochlea).

Section 8 — Temporal Development

Onset: retinal disease childhood/adolescence (insidious, chronic); hearing loss post-lingual with variable, often adult, onset. Progression: slowly progressive; legal blindness ~mid-adulthood; SNHL progressive. Course: chronic, lifelong, progressive; no remission. Critical period: early diagnosis enables timely cochlear implantation and low-vision planning before severe dual sensory loss.

Section 9 — Inheritance and Population

Inheritance: autosomal recessive. Penetrance: high for the sensory phenotype (variable expressivity of the hearing and fertility components). Epidemiology: ultra-rare; prevalence/incidence not formally established (only several dozen confirmed cases worldwide). Founder effects: Jewish-ancestry CEP78 truncating alleles; Belgian/German p.Leu150Ser missense allele. Consanguinity contributes (homozygosity mapping). Sex ratio: retinal/auditory phenotype affects both sexes equally; fertility reduction affects males only.

Section 10 — Diagnostics

Full-field ERG (cone-rod pattern), OCT, fundus autofluorescence, adaptive optics, pure-tone audiometry, and molecular testing (retinal-dystrophy gene panels, WES, WGS). WES/WGS or panels are needed to detect deep-intronic/splice variants of these ciliary genes. Differential diagnosis: Usher syndrome (rod-first, congenital HL), Usher IV/ARSG, PHARC/ABHD12, TUBB4B-LCA, Alström syndrome, Heimler syndrome. Screening: carrier/cascade testing in founder populations; no newborn screening exists.

Section 11 — Outcome/Prognosis

Survival/mortality: normal life expectancy — CRDHL is not life-limiting. Morbidity: major — progressive dual sensory disability. Prognosis: legal blindness by ~mid-adulthood (cone-rod natural history); progressive SNHL. Recovery: no spontaneous recovery of vision or hearing; cochlear implantation rehabilitates the auditory component. Prognostic factors: allele type (null vs hypomorphic) may influence severity, though genotype-phenotype correlations remain to be established.

Section 12 — Treatment

Pharmacotherapy/advanced therapeutics: none disease-specific (no approved gene/RNA/cell therapy). Supportive/rehabilitative: low-vision aids, hearing aids, cochlear implantation (NCIT — cochlear implant procedure), genetic counseling. Experimental: gene-augmentation and splice-correction approaches are conceptually attractive but not yet in trials for CEP78. Treatment strategy: multidisciplinary (ophthalmology, audiology/otology, medical genetics, reproductive medicine).

Section 13 — Prevention

Primary prevention: genetic/carrier screening and counseling in at-risk families and founder populations; prenatal/preimplantation genetic testing where desired. Secondary prevention: early molecular diagnosis to enable timely cochlear implantation and low-vision support. Tertiary prevention: rehabilitation to preserve function. No vaccine, behavioral, or environmental interventions apply.

Section 14 — Other Species / Natural Disease

Model species: Mus musculus (NCBI Taxon:10090) — Cep78-knockout. Orthologs exist across vertebrates (Cep78). No naturally occurring companion-animal CEP78-CRDHL is documented; however, the differential-diagnosis gene ARSG has naturally occurring canine and murine neuronal ceroid lipofuscinosis models. No zoonotic potential (genetic disease).

Section 15 — Model Organisms

Mammalian: Cep78-knockout mouse (recapitulates male infertility/OAT; retinal/auditory phenotyping limited). Cellular/in vitro: patient dermal fibroblasts and nasal-epithelial brushings (elongated primary cilia, reduced protein stability); HeLa/RPE cultured cells (centriolar localization, VprBP interaction, CEP350-FOP recruitment). Limitations: no validated model of the retinal or cochlear sensory phenotype; retinal organoids and iPSC-derived otic organoids are logical future resources.

Mechanistic Model / Interpretation

CRDHL is best understood as a centriole/cilium homeostasis disorder in which loss of CEP78 selectively injures the body's most centriole- and cilium-dependent post-mitotic cells. The following ordered causal chain integrates the confirmed findings; each step is annotated as demonstrated or inferred.

STEP 1 (demonstrated)
  Biallelic CEP78 loss-of-function / destabilizing variants
  (nonsense, frameshift, splice, or missense — e.g. p.Asp298Valfs*17, p.Leu150Ser)
│  reduce or abolish functional CEP78 protein
▼
STEP 2 (demonstrated in vitro)
  Loss of CEP78 at the distal centriole disrupts:
    • the CEP350–FOP–CEP78 centriole-length-control module
    • the EDD–DYRK2–DDB1 ubiquitin-ligase axis (via VprBP)
│  perturbs centrosome homeostasis
▼
STEP 3 (demonstrated in patient cells; extrapolated to specialized cilia = inferred)
  Abnormal centriole/basal-body and ciliary axoneme assembly
  (elongated primary cilia in patient fibroblasts & nasal brushings)
│
├───────────────► STEP 4a (inferred) — RETINA
│     Defective connecting-cilium transport in cone/rod
│     photoreceptors → progressive photoreceptor dysfunction
│     and death, CONE-PREDOMINANT (CEP78 enriched in cone
│     inner segments)  →  CONE-ROD DYSTROPHY
│
├───────────────► STEP 4b (inferred) — COCHLEA
│     Kinocilium/basal-body dysfunction in cochlear hair cells
│     →  BILATERAL PROGRESSIVE SENSORINEURAL HEARING LOSS
│
└───────────────► STEP 4c (demonstrated in mouse; human sperm abnormalities)
      Flagellar axoneme/centriole defects in spermatids
      →  OLIGOASTHENOTERATOZOOSPERMIA / MALE SUBFERTILITY

ENDPOINT: Cone-rod dystrophy + progressive bilateral SNHL ± reduced male fertility

Upstream vs downstream. Steps 1–2 (protein loss → centrosome dysregulation) are upstream and shared across all tissues. Steps 4a–4c are downstream, tissue-specific manifestations of the same lesion. The cone-predominance of the retinal phenotype is explained by the higher expression of CEP78 in cone inner segments than in rods — a rare instance where the molecular expression pattern directly predicts the clinical phenotype.

Supporting quotes:

"deregulation of centrosome homeostasis is a hallmark feature of many human diseases" — PMID: 28242748

"The CEP350-FOP complex in association with CEP78 or OFD1 controls centriole microtubule length." — PMID: 36315013

Ontology term suggestions:

Evidence Base

Note on citation integrity: Two citation snippets attributed to PMID: 39747485 were flagged as mismatch during verification (the exact wording could not be confirmed against the stored abstract). The mouse-model conclusion is corroborated by the paper's title, "Cep78 knockout causes sterility and oligoasthenoteratozoospermia in male mice," and an associated author correction (PMID: 40075211); readers should treat the specific quoted phrasing with caution.

Limitations and Knowledge Gaps

1. Small evidence base. CRDHL is ultra-rare (several dozen molecularly confirmed cases). Prevalence and incidence figures are not established; no formal epidemiological registry exists. Penetrance and expressivity estimates are qualitative.
2. Inferred tissue mechanisms. The retinal (Step 4a) and cochlear (Step 4b) mechanistic steps are inferred by extrapolation from the demonstrated ciliary/centriolar defect in accessible cells (fibroblasts, nasal brushings) and from expression data. Direct demonstration of connecting-cilium or hair-cell kinocilium dysfunction in CEP78-deficient photoreceptors or cochlear cells has not been reported.
3. Hearing-loss natural history is under-characterized. Onset, audiometric progression rate, and severity of SNHL in CEP78-CRDHL are variably reported; some patients have "presumed normal hearing" in adolescence, implying delayed onset that may not yet be captured.
4. Cochlear-implant evidence is indirect. CI benefit is extrapolated from Usher type IIa and syndromic-deafness cohorts, not from CEP78-CRDHL patients specifically.
5. No CEP78 retinal/cochlear animal model. The existing Cep78-knockout mouse recapitulates male infertility but published retinal or auditory phenotyping of this model is limited; a validated model of the sensory phenotype is a gap.
6. Modifier genes, epigenetics, and gene-environment interactions are essentially unstudied for this disorder. No protective alleles, environmental risk factors, or infectious triggers apply (this is a monogenic Mendelian disorder).
7. Verification caveat on the Cep78-KO mouse quote (see Evidence Base note).

Proposed Follow-up Experiments / Actions

1. Generate and phenotype a retina/cochlea-focused Cep78 model. Characterize photoreceptor connecting cilia and cochlear hair-cell kinocilia in Cep78-knockout or conditional/knock-in mice (or in patient-derived retinal organoids and iPSC-derived otic organoids) to convert the inferred Steps 4a/4b into demonstrated mechanisms.
2. Assemble a CEP78/CEP250 patient registry with standardized longitudinal ERG, OCT, and pure-tone audiometry to define quantitative natural history (age at legal blindness; audiometric slope; SNHL onset distribution) and penetrance of the fertility phenotype.
3. Prospectively evaluate cochlear implantation specifically in CEP78-CRDHL patients, using phoneme/speech-perception scores benchmarked against the Usher CI literature.
4. Deep structural/functional analysis of the p.Leu150Ser missense allele and other missense variants to establish genotype-phenotype correlations (null vs. hypomorphic) that may predict severity and residual function — relevant for future variant classification (ACMG/AMP) and therapy eligibility.
5. Assess gene-augmentation feasibility. CEP78 is a relatively small centriolar gene; explore AAV-mediated gene replacement or antisense/splice-correction approaches (e.g., for the recurrent c.893-1G>A splice allele) in patient cells and organoids as a proof-of-concept therapeutic strategy.
6. Screen for CEP78/CEP250 founder alleles in relevant populations (Jewish-ancestry, Belgian/German cohorts) via carrier screening and cascade testing to inform genetic counseling.

Consensus Answer

Cone-Rod Dystrophy and Hearing Loss (CRDHL; MONDO:0014980, OMIM #617236) is a rare autosomal recessive ciliopathy caused primarily by biallelic loss-of-function of CEP78, a distal-centriole protein controlling centriole length and centrosome homeostasis, with an overlapping second locus in CEP250. Loss of CEP78 disrupts the specialized cilia and centriole-derived structures of the most centriole-dependent post-mitotic cells, producing childhood-onset cone-predominant cone-rod dystrophy (legal blindness by mid-adulthood), bilateral post-lingual progressive sensorineural hearing loss, and reduced male fertility in some patients — a phenotype distinct from rod-first Usher syndrome. There is no disease-specific therapy; management is supportive (hearing aids/cochlear implantation, low-vision rehabilitation, genetic counseling), with diagnosis by ERG/OCT plus audiometry and panel/exome sequencing.

Artifacts

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Reference Validation

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All extracted references resolved successfully.

Term Validation

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

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:0000548 (2 mentions) - the report calls it "Clinical sign", "Cone-rod dystrophy"; HP calls it Cone/cone-rod dystrophy
• HP:0000407 (2 mentions) - the report calls it "Clinical sign / lab (audiometry)", "Sensorineural hearing impairment"; HP calls it Sensorineural hearing impairment
• HP:0000618 (2 mentions) - the report calls it "Clinical sign"; HP calls it Blindness

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:

• CL:0000855 (2 mentions) - the report calls it "Cochlear/inner ear hair cell"; CL calls it sensory hair cell
• CL:0000019 (2 mentions) - the report calls it "Sperm / male germ cell"; CL calls it sperm, and lists "sperm cell" among its other names

Terms named inconsistently

The report gives these identifiers more than one name of its own:

• HP:0000548 - called "Clinical sign", "Cone-rod dystrophy"
• HP:0000407 - called "Clinical sign / lab (audiometry)", "Sensorineural hearing impairment"

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: Taxon.