| Domain | Evidence-based finding | Quantitative data | Suggested ontology IDs/terms | Evidence limitations |
|---|---|---|---|---|
| Identifiers | Disease resolves to DNAJC30-associated autosomal recessive Leber hereditary optic neuropathy, also called LHONAR1 / arLHON; Open Targets links the entity to MONDO_0958183 and DNAJC30; OMIM phenotype reported as 619382. Information here is disease-level synthesis from published cohorts/case series, not EHR-derived. (pqac-00000000, pqac-00000006, pqac-00000010) | MONDO:0958183; OMIM:619382 | MONDO:0958183; Leber-like hereditary optic neuropathy, autosomal recessive 1 | Orphanet, ICD, MeSH identifiers were not established in the retrieved evidence set. |
| Gene / variants | Causal gene is DNAJC30. Recurrent founder variant c.152A>G (p.Tyr51Cys) is the predominant disease allele; additional pathogenic/likely pathogenic variants reported include c.610G>T (p.Glu204*), c.230_232del (p.His77del), c.293A>G (p.Tyr98Cys), c.293A>C (p.Tyr98Ser), and c.130_131delTC (p.Ser44ValfsTer8). (pqac-00000000, pqac-00000002, pqac-00000004, pqac-00000007, pqac-00000008, pqac-00000009) | c.152A>G accounts for ~90% of disease alleles in Central Europe and ~95% of alleles in the Polish cohort; gnomAD frequency for p.Tyr51Cys reported as 0.12% with no homozygotes reported in Stenton 2022. (pqac-00000003, pqac-00000008, pqac-00000009) | HGNC: DNAJC30; Sequence variants as HGVS terms | No ClinVar accession numbers or HGNC numeric gene ID were provided in retrieved contexts. |
| Inheritance | Inheritance is autosomal recessive with biallelic DNAJC30 variants. Penetrance is incomplete and sex-dependent, with marked male predominance among manifesting patients. (pqac-00000008, pqac-00000011) | In one Central European cohort, 5/35 patients were female (14.3%), ~6:1 male:female. Two asymptomatic homozygous carriers were reported in Stenton 2022. (pqac-00000001, pqac-00000004, pqac-00000008) | HP:0000007 Autosomal recessive inheritance; HP:0001411 Decreased penetrance | Formal penetrance percentage was not established in retrieved evidence. |
| Epidemiology / population | arLHON due to DNAJC30 is a recurrent cause of inherited optic neuropathy in Central/Eastern Europe and may be particularly common in Poland because of a founder effect. (pqac-00000002, pqac-00000003, pqac-00000009) | 35/1202 screened Central European patients carried likely pathogenic DNAJC30 variants (2.9% detection rate); DNAJC30 accounted for 7.7% of LHON cases in one database; across European centers, DNAJC30 variants accounted for 4-27% of genetically confirmed LHON in the cited synthesis. (pqac-00000001, pqac-00000005, pqac-00000012) | Population descriptor only; no ontology ID established | No population-based prevalence or incidence per 100,000 was established. Data are referral/cohort based and geographically enriched. |
| Phenotype | Core presentation closely mimics mtDNA-LHON: painless subacute central visual loss, dyschromatopsia, central/cecocentral scotoma, optic disc microangiopathy early and temporal optic atrophy later. Bilateral involvement is the rule at follow-up. (pqac-00000003, pqac-00000004, pqac-00000009) | Central/cecocentral field defects 96.6%; papillary microangiopathy 94.1%; temporally accentuated optic atrophy 91.7%; color vision disturbance 68.8%; bilateral onset 40%, unilateral then fellow-eye involvement 60%, all bilateral at follow-up. (pqac-00000003, pqac-00000004) | HP:0000648 Optic atrophy; HP:0000572 Loss of visual acuity; HP:0000555 Visual field defect; HP:0001098 Abnormality of color vision; HP:0007686 Scotoma; HP:0012800 Bilateral visual impairment | Detailed HPO mapping for fundus microangiopathy and OCT/VEP findings was not fully established from retrieved evidence. |
| Onset / course | Typically juvenile-to-young-adult onset, earlier than mtDNA-LHON, with subacute progression and relatively frequent spontaneous or treatment-associated recovery. (pqac-00000003, pqac-00000008, pqac-00000009) | Mean/median onset about 18.5-19 years; reported range 9.5-45.1 years in Central Europe; one Polish case onset at 68 years. Median interval between eyes 3.5 weeks (range 1-17) in one subset. Spontaneous complete recovery of remaining vision reported in 45% at median 19 months in one cohort. (pqac-00000001, pqac-00000003, pqac-00000009) | HP:0003596 Middle age onset not typical; HP:0011462 Young adult onset; course descriptors not uniquely ontologized here | Staging schema is not established; recovery definitions vary across studies. |
| Mechanism / pathophysiology | DNAJC30 encodes a mitochondrial chaperone implicated in respiratory-chain complex I maintenance/repair/turnover; loss leads to isolated complex I deficiency, impaired ATP-linked bioenergetics and likely increased oxidative stress, producing selective retinal ganglion-cell vulnerability analogous to LHON biology. DNAJC30 also has reported interaction with ATP synthase/complex V. (pqac-00000006, pqac-00000008, pqac-00000011) | Near-complete loss of DNAJC30 protein expression reported for the founder variant; patient/Leigh cases showed isolated RCCI deficiency on enzyme analysis. (pqac-00000008, pqac-00000012) | GO:0005747 mitochondrial respiratory chain complex I; GO:0006119 oxidative phosphorylation; GO:0006979 response to oxidative stress; GO:0006091 generation of precursor metabolites and energy | Much downstream ROS/RGC apoptosis detail is inferred from broader LHON biology rather than directly quantified in DNAJC30 patient retina. |
| Anatomy / cells / subcellular location | Primary affected tissue is the optic nerve/retinal ganglion cell pathway. Subcellular localization is mitochondrial, especially respiratory-chain machinery. (pqac-00000006, pqac-00000011) | Bilateral optic neuropathy predominates; extraocular manifestations absent in most arLHON cases, but Leigh syndrome and occasional motor features were reported in a minority. (pqac-00000002, pqac-00000004, pqac-00000008) | UBERON:0000966 retina; UBERON:0000390 optic nerve; CL:0000705 retinal ganglion cell; GO:0005739 mitochondrion; GO:0005743 mitochondrial inner membrane | No direct retinal histopathology or single-cell localization studies were identified for this disease. |
| Diagnostics | Diagnosis relies on clinical recognition of LHON-like optic neuropathy plus molecular confirmation of biallelic DNAJC30 variants. DNAJC30 screening is recommended in mtDNA-negative LHON, especially in Central/Eastern European patients; because DNAJC30 is single exon, Sanger sequencing can be a practical first test in Poland. (pqac-00000002, pqac-00000005, pqac-00000009) | Central European detection rate 2.9% (35/1202). In the Polish study, 46 clinically diagnosed LHON patients had DNAJC30 findings and 32 were diagnosed after DNAJC30 testing was introduced locally. (pqac-00000005, pqac-00000009) | Diagnostic concepts: molecular genetic testing; ophthalmic exam; visual field testing; OCT/VEP not fully ontologized here | No disease-specific formal diagnostic criteria, biomarker panel, or screening guideline were retrieved. |
| Prognosis | Compared with mtDNA-LHON, DNAJC30 arLHON generally shows better visual prognosis, including higher spontaneous recovery and more favorable idebenone-associated outcomes. (pqac-00000002, pqac-00000008, pqac-00000012) | Median visual acuity improved from 1.3 logMAR at nadir to 0.5 logMAR at last visit in one cohort; clinically relevant recovery with idebenone in at least one eye 77% in arLHON versus 43% in mtLHON; spontaneous recovery 69% untreated arLHON versus 30% untreated mtLHON. (pqac-00000003, pqac-00000012) | Outcome terms: visual recovery; optic atrophy | No survival, mortality, or life-expectancy estimates specific to isolated arLHON were established. Leigh-spectrum cases likely have different prognosis. |
| Treatment | No DNAJC30-specific approved therapy exists. Idebenone is the principal disease-directed treatment used in practice by extrapolation from LHON and supported by observational DNAJC30 data suggesting higher recovery rates/shorter recovery time. Low-vision/visual rehabilitation is supportive standard care. MT-ND4 gene therapy trials are not genotype-matched for DNAJC30 disease. (pqac-00000002, pqac-00000012, pqac-00000013) | No randomized DNAJC30-specific trial identified; one Central European patient had taken idebenone for 6 months but recovered before treatment initiation; observational cohort comparisons favored idebenone-treated arLHON. (pqac-00000003, pqac-00000012) | NCIT:C952 Idebenone; NCIT terms for low vision rehabilitation/supportive care if used in downstream curation | Evidence is observational and partly extrapolated from mtDNA-LHON; no DNAJC30-targeted interventional trial was retrieved. |
| Prevention / counseling | Primary prevention is not established. Practical prevention focuses on genetic counseling, carrier/family testing, and reproductive counseling for an autosomal recessive condition. General LHON advice on smoking/alcohol avoidance may be reasonable but is extrapolated, not disease-specific evidence. (pqac-00000011, pqac-00000013) | Not established quantitatively for DNAJC30 arLHON | HP:0000007 Autosomal recessive inheritance; carrier testing/cascade testing concepts | No disease-specific studies of environmental triggers, protective factors, prenatal screening uptake, or PGT outcomes were retrieved. |
| Other species / natural disease | No naturally occurring veterinary disease equivalent was established from retrieved evidence. (pqac-00000000) | Not established | NCBI Taxon IDs not established | Evidence absent in retrieved set. |
| Model organisms / experimental systems | Disease mechanism is supported mainly by patient-based biochemical evidence and broader mitochondrial functional studies; no validated DNAJC30-specific optic-neuropathy animal model was established in the retrieved evidence. Leigh-spectrum/digenic observations suggest useful mechanistic complexity but not a dedicated model system. (pqac-00000008, pqac-00000011) | Not established | Experimental system concepts: patient fibroblasts; mitochondrial enzyme assay | Model-organism availability, recapitulation fidelity, and resource identifiers were not established from retrieved sources. |


*Table: This table condenses the current evidence base for DNAJC30-associated autosomal recessive Leber hereditary optic neuropathy into knowledge-base-ready domains. It highlights what is well supported by cohort data and what remains unknown or only extrapolated from broader LHON literature.*