| Domain | Established finding | Evidence type | Ontology/identifier suggestions |
|---|---|---|---|
| Disease identity | Autosomal recessive nonsyndromic hearing loss 30 (DFNB30), a Mendelian nonsyndromic sensorineural hearing-loss disorder | Aggregated disease-resource association plus human molecular genetics (pqac-00000000) | MONDO:0011774; synonym: DFNB30 |
| Causal gene | Biallelic loss-of-function or damaging variants in **MYO3A** (myosin IIIA) cause DFNB30; heterozygous dominant MYO3A disease is a distinct allelic disorder (pqac-00000000, pqac-00000005, pqac-00000006) | Human pedigrees, sequencing, segregation, functional studies | MYO3A; OMIM gene 606808; Ensembl ENSG00000095777 |
| Inheritance | Autosomal recessive; affected individuals are homozygous or compound heterozygous, whereas heterozygous relatives are generally carriers unless they harbor a distinct dominant-acting allele | Human family segregation (pqac-00000005, pqac-00000006) | Autosomal recessive inheritance; germline variant |
| Core phenotype | Bilateral, nonsyndromic, progressive sensorineural hearing loss, often initially affecting high frequencies; reported onset ranges from congenital to the second decade and may ultimately reach severe-to-profound levels (pqac-00000002, pqac-00000005, pqac-00000012) | Human clinical audiology and cohorts | Sensorineural hearing impairment; bilateral hearing impairment; progressive hearing impairment; high-frequency hearing impairment; profound hearing impairment |
| Anatomy and mechanism | MYO3A localizes near the tips of cochlear and vestibular hair-cell stereocilia. Impaired actin-based motor/cargo regulation disrupts stereocilia length, spacing, staircase organization, and consequently mechanotransduction (pqac-00000006, pqac-00000011, pqac-00000012) | Hair-cell studies, biochemical/cellular assays, mouse models; final mechanotransduction link partly inferred | Cochlea; organ of Corti; inner and outer hair cell; stereocilium; actin cytoskeleton; sensory perception of sound |
| Epidemiology | Nine candidate individuals were found among 15,684 Japanese hearing-loss referrals—**0.06% of that referral cohort**, not population prevalence (pqac-00000001, pqac-00000002) | 2025 multicenter referral-cohort sequencing study | Rare disease; prevalence among hearing-loss referrals |
| Diagnosis | Confirm sensorineural loss and progression with age-appropriate audiometry, otoacoustic emissions and/or auditory brainstem response, then identify pathogenic/likely pathogenic variants on both MYO3A alleles using a comprehensive hearing-loss panel, exome, or genome sequencing with segregation and copy-number analysis as appropriate (pqac-00000003, pqac-00000011, pqac-00000014) | Clinical audiology plus molecular diagnosis; general hereditary-hearing-loss practice | Pure-tone audiometry; auditory brainstem response; otoacoustic emission; molecular genetic testing; biallelic genotype |
| Current management | No disease-modifying MYO3A-specific treatment is established. Management follows hearing-loss severity and communication needs: serial audiology, hearing aids, cochlear implantation when indicated, and speech/language, auditory, educational, or sign-language support | Standard-of-care extrapolation from nonsyndromic sensorineural hearing loss; not tested specifically in DFNB30 | Hearing aid; cochlear implantation; audiologic rehabilitation; speech-language therapy |
| Experimental therapy | No MYO3A-targeted gene, RNA, cell, or pharmacologic therapy trial was identified; current hereditary-hearing-loss gene-therapy trials target other genes and should not be represented as DFNB30 trials | Clinical-trial search and literature review | Gene therapy—investigational; no DFNB30-specific intervention |
| Model organisms | MYO3A loss-of-function mouse models develop progressive hearing loss beginning at high frequencies and later involving broader frequencies, with abnormal stereocilia; combined Myo3a/Myo3b loss produces a stronger phenotype, indicating partial redundancy (pqac-00000005, pqac-00000006, pqac-00000011) | Knock-in/knockout mouse models | Mus musculus; Myo3a knock-in/knockout; auditory hair cell; abnormal stereocilium morphology |


*Table: Concise evidence-based summary of DFNB30 identity, phenotype, mechanism, frequency, diagnosis, management, and models. It separates established disease-specific findings from standard-care extrapolation and investigational gaps.*