| Domain | Item | Suggested ontology mapping(s) | Key details for KB entry | Evidence level | Citations |
|---|---|---|---|---|---|
| Disease identifiers | Cone-rod dystrophy and hearing loss 2 | MONDO:0020780; OMIM: 618358 | Rare Mendelian oto-retinal disorder linked to biallelic CEP250; often described as atypical Usher-like disease rather than classic Usher subtype | Direct human disease-level resource and case-series context | (pqac-00000013, pqac-00000014, pqac-00000022) |
| Synonyms | CEP250-related CRDHL2; atypical Usher syndrome; Usher-like disease; cone-rod dystrophy with sensorineural hearing loss | Suggested synonym set only | Literature uses overlapping labels; disease boundaries remain somewhat fluid because CEP250 alleles can also present as nonsyndromic RP or nonsyndromic hearing loss | Direct human, with nomenclature caveat | (pqac-00000016, pqac-00000022) |
| Core phenotype | Progressive sensorineural hearing loss | Suggested HPO: Sensorineural hearing impairment HP:0000407; Progressive hearing impairment HP:0001731 | Human CEP250 series: onset reported from <10 to 24 years; RP1973 had bilateral moderate-severe progressive hearing loss starting at age 13; no vestibular symptoms reported in the 2021 series | Direct human | (pqac-00000015, pqac-00000021) |
| Core phenotype | Mild cone-predominant retinal dysfunction / cone-rod dystrophy spectrum | Suggested HPO: Cone-rod dystrophy HP:0000548; Cone dystrophy HP:0000547; Abnormality of electroretinogram HP:0001311 | Age of ocular onset in CEP250 cases ranged 13-30 years in multicenter series; one tested patient showed mild cone dystrophy with normal rod function on ffERG; literature also includes late-onset cone-rod dystrophy | Direct human | (pqac-00000015, pqac-00000013, pqac-00000022) |
| Core phenotype | Photophobia and reduced visual acuity | Suggested HPO: Photophobia HP:0000613; Reduced visual acuity HP:0007663 | RP1973 had late-onset progressive visual decline with photophobia; BCVA in CEP250 series ranged about 20/60 to 20/200 | Direct human | (pqac-00000021, pqac-00000015) |
| Core phenotype | Subtle to mild retinal structural abnormality | Suggested HPO: Outer retinal atrophy HP:0030498; Thinning of outer nuclear layer HP:0033667; Abnormal fundus autofluorescence HP:0030636 | Color fundus may be normal or mildly abnormal; FAF showed subtle peripheral/peripapillary changes; OCT showed outer retinal atrophy, ONL thinning, and subtle EZ/IZ disruption | Direct human | (pqac-00000015, pqac-00000021) |
| Core phenotype | Retinitis pigmentosa-like fundus changes in some cases | Suggested HPO: Retinitis pigmentosa HP:0000510; Bone spicule pigmentation of the retina HP:0007703; Attenuated retinal blood vessels HP:0007763 | RP1973 showed mid-peripheral bone-spicule pigment migration and narrowed peripheral vessels, supporting overlap with RP/Usher-like phenotypes | Direct human | (pqac-00000021) |
| Core phenotype | Vestibular involvement | Suggested HPO: Abnormal vestibular function HP:0001751 | No vestibular symptoms were reported in the CEP250 patients of the 2021 multicenter series; vestibular dysfunction therefore appears absent or uncommon in currently described CRDHL2 cases | Direct human negative finding | (pqac-00000015) |
| Gene / protein | CEP250 / C-Nap1 | HGNC gene symbol: CEP250; OMIM gene: 609689 | Encodes centrosome-associated C-Nap1, a centrosome linker/cohesion protein also localized in photoreceptor/basal-body contexts | Human molecular + broader cell biology | (pqac-00000016, pqac-00000017) |
| Inheritance | Autosomal recessive | Suggested HPO: Autosomal recessive inheritance HP:0000007 | Disease is associated with biallelic CEP250 variants; reported affected individuals include homozygous and compound-heterozygous cases | Direct human | (pqac-00000013, pqac-00000015, pqac-00000021) |
| Variant spectrum relevant to CRDHL2 | Truncating alleles predominate | Suggested sequence ontology classes: nonsense_variant, frameshift_variant | All CEP250 variants in the 2021 atypical Usher cohort were novel nonsense or frameshift variants; reported syndromic examples include p.R1155*, p.K1113*, p.R1336*, and Japanese family compound heterozygous nonsense variants | Direct human, partially summarized across studies | (pqac-00000015, pqac-00000013, pqac-00000022, pqac-00000002) |
| Allelic heterogeneity caveat | Nonsyndromic RP or nonsyndromic hearing loss can also result from CEP250 variants | Suggested note, not ontology assertion | Missense and some nonsense alleles have been reported in nonsyndromic RP or progressive hearing loss without retinal degeneration at time of report; genotype-phenotype correlation remains incomplete | Direct human with caution | (pqac-00000016, pqac-00000017, pqac-00000003) |
| Organ / system | Eye / retina | Suggested UBERON: retina UBERON:0000966; eye UBERON:0000970 | Primary visual tissue affected; human imaging points to outer retina involvement | Direct human | (pqac-00000015, pqac-00000021) |
| Organ / system | Inner ear / cochlea | Suggested UBERON: inner ear UBERON:0001844; cochlea UBERON:0001853 | Primary auditory tissue affected; progressive SNHL is a core disease manifestation | Direct human; mouse supports tissue localization | (pqac-00000015, pqac-00000016, pqac-00000018) |
| Tissue / cell type | Photoreceptors | Suggested CL: photoreceptor cell CL:0000679; rod photoreceptor cell CL:0000604; cone photoreceptor cell CL:0000710 | Human ffERG and OCT support photoreceptor dysfunction, with cone involvement possibly greater in some cases | Direct human; mouse mechanistic support | (pqac-00000015, pqac-00000019) |
| Tissue / cell type | Cochlear hair cells | Suggested CL: auditory hair cell CL:0000589; inner hair cell / outer hair cell suggested | Cep250 is expressed in murine inner and outer hair cells; knockout models show hair-cell degeneration and high-frequency hearing loss | Mouse/in vitro inference supporting human auditory phenotype | (pqac-00000016, pqac-00000018) |
| Subcellular compartment | Centrosome / centriole proximal end / basal body / ciliary region | Suggested GO CC: centrosome GO:0005813; centriole GO:0005814; basal body GO:0005932; ciliary basal body suggested | C-Nap1 is a centrosomal linker protein; human variant p.Gln1171Ter mislocalized from centrosome to cytosol in NIH3T3 cells; literature places CEP250 in photoreceptor ciliary/basal-body contexts | In vitro + broader biology; indirect for CRDHL2 | (pqac-00000016, pqac-00000017, pqac-00000004) |
| Biological process | Centrosome cohesion / ciliogenesis / cilium organization | Suggested GO BP: centrosome cycle / centrosome cohesion suggested; cilium organization GO:0044782; ciliogenesis suggested | Mechanistic model: loss of C-Nap1 disrupts centrosome localization/cohesion and ciliary homeostasis, impairing photoreceptor and hair-cell maintenance | In vitro + mouse inference | (pqac-00000016, pqac-00000017, pqac-00000004) |
| Biological process | Photoreceptor degeneration and apoptosis | Suggested GO BP: photoreceptor cell maintenance suggested; apoptotic process GO:0006915 | Cep250-deficient retina shows reduced photoreceptors and increased TUNEL positivity in mice | Mouse inference | (pqac-00000019, pqac-00000006) |
| Biological process | Stress/signaling dysregulation in retina | Suggested GO/Pathway terms: MAPK cascade GO:0000165; cyclic nucleotide signaling suggested | RNA-seq in Cep250 KO retina found 149 upregulated and 149 downregulated genes; enriched pathways included cGMP-PKG, MAPK, edn2-fgf2 axis, thyroid hormone synthesis; ER protein processing downregulated | Mouse inference | (pqac-00000019, pqac-00000011) |
| Diagnostics | Molecular diagnosis | Suggested NCIT: Genetic Testing; Whole Exome Sequencing; Targeted Next-Generation Sequencing Panel | WES and targeted high-throughput panels have identified causal biallelic CEP250 variants; useful especially in atypical Usher/dual sensory phenotypes | Direct human real-world implementation | (pqac-00000016, pqac-00000022, pqac-00000014) |
| Diagnostics | Ophthalmic functional testing | Suggested NCIT: Electroretinography | ffERG can show mild cone dystrophy with normal rod function in some human CEP250 cases; useful for disease characterization | Direct human | (pqac-00000015) |
| Diagnostics | Retinal imaging | Suggested NCIT: Optical Coherence Tomography; Fundus Autofluorescence Imaging; Fundus Photography; Visual Field Examination | Human cases showed OCT outer retinal atrophy/ONL thinning/EZ-IZ disruption and subtle FAF abnormalities; visual fields may range from near-normal wide fields to marked constriction | Direct human | (pqac-00000015, pqac-00000021, pqac-00000014) |
| Diagnostics | Audiologic testing | Suggested NCIT: Pure Tone Audiometry; Auditory Brainstem Response | Progressive SNHL is central; pure-tone audiograms used clinically in human hearing studies; ABR is established in mouse models and can support translational studies | Human + mouse | (pqac-00000016, pqac-00000013, pqac-00000018) |
| Differential diagnosis | Classic Usher syndrome types 1-3; CEP78-, ARSG-, ABHD12-related atypical Usher; nonsyndromic RP; nonsyndromic AR hearing loss | Suggested note | Clinical overlap is substantial; genotype-first evaluation is recommended in atypical presentations combining retinal disease with progressive SNHL | Direct human | (pqac-00000014, pqac-00000015, pqac-00000022) |
| Management | Sensory surveillance and supportive care | Suggested NCIT: Ophthalmologic Examination; Audiologic Monitoring; Genetic Counseling | No CEP250-specific disease-modifying therapy identified; current care centers on longitudinal eye/hearing follow-up and counseling | Direct evidence for absence of targeted therapy; standard-of-care inference | (pqac-00000012, pqac-00000022) |
| Management | Hearing rehabilitation | Suggested NCIT: Hearing Aid Device; Cochlear Implantation | Disease-specific CEP250 outcome data not identified, but progressive SNHL makes standard hearing rehabilitation relevant in practice | Indirect clinical inference | (pqac-00000012, pqac-00000016) |
| Management | Low-vision and disability support | Suggested NCIT: Low Vision Rehabilitation; Assistive Device | Disease-specific studies absent, but visual acuity loss, photophobia, and retinal degeneration support standard low-vision measures | Indirect clinical inference | (pqac-00000015, pqac-00000021) |
| Advanced therapeutics | Gene therapy / RNA therapy / trials | Suggested NCIT: Gene Therapy | No CEP250-specific interventional trial or approved therapy was identified in gathered evidence; mouse models were proposed as platforms for future therapy development | Negative evidence + preclinical rationale | (pqac-00000010, pqac-00000012) |
| Evidence caveat | Human evidence base is very small | Suggested note | Current phenotype definition relies on a small number of families/cases, plus retrospective multicenter aggregation of only three CEP250 patients in one series | Direct human caveat | (pqac-00000015, pqac-00000022) |
| Evidence caveat | Variant-phenotype correlation remains unresolved | Suggested note | Truncating alleles are enriched in syndromic cases, but CEP250 can also underlie nonsyndromic retinal or auditory disease; penetrance and age dependence are not yet well quantified | Direct human caveat | (pqac-00000016, pqac-00000017, pqac-00000003) |
| Evidence caveat | Epidemiology and modifiers largely unavailable | Suggested note | No robust disease-specific prevalence, incidence, penetrance, sex ratio, environmental modifiers, or protective factors were identified in the gathered literature | Absence of evidence | (pqac-00000012) |


*Table: This table condenses the gathered evidence into a compact knowledge-base crosswalk for CEP250-associated CRDHL2, linking phenotype, anatomy, mechanism, diagnostics, and management to suggested ontology terms. It also flags where statements are supported directly by human data versus mouse or in-vitro inference.*