Autosomal Dominant Nonsyndromic Hearing Loss 47

Mendelian MONDO:0012090 Pathograph 3 Show in embeddings browser Autosomal Dominant Nonsyndromic Hearing Loss

DFNA47 is a mapped-but-gene-unidentified locus (9p21-22) for autosomal dominant, postlingual, progressive, nonsyndromic sensorineural hearing loss, reported in a single large Italian kindred in 2003. No causal gene has been cloned in the two decades since. This entry is deliberately narrow: it records the locus mapping, the clinical/audiometric natural history reported in the founding family, and why the candidate gene MYO1A is excluded (MYO1A is the gene for a different locus, DFNA48, and its disease association has itself since been refuted) rather than attributing a molecular mechanism, cell type, or targeted treatment the literature does not support.

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1
Inheritance
1
Pathophys.
2
Phenotypes
3
Pathograph
1
Genes
3
Medical Actions
1
Deep Research
👪

Inheritance

1
Autosomal dominant HP:0000006
Autosomal dominant, mapped by linkage in the single reported Italian kindred. A heterozygous affected parent has a 50% probability of transmitting the disease haplotype per pregnancy. Penetrance is not stated in the accessible primary report or the 2023 review's summary of this locus, so no penetrance claim is made here.
Autosomal dominant inheritance
Show evidence (1 reference)
PMID:12634859 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"Here we report the mapping of a novel locus for autosomal dominant non-syndromic hearing loss, DFNA47, to chromosome 9p21-22 in a large multigenerational Italian family with progressive hearing impairment."
Establishes the dominant mode of transmission and the founding linkage mapping to the 9p21-22 locus.
⚙

Pathophysiology

1
Progressive Cochlear Dysfunction at an Unidentified Molecular Target
Mechanism confidence: Hypothetical
No causal gene, transcript, or protein has been identified for DFNA47 despite the locus having been mapped by linkage analysis in 2003, so no molecular pathway, cellular process, or protein-level mechanism can be attributed to it. The only mechanistic inference available is drawn from the clinical audioprofile itself: hearing loss in the founding family began after the teenage years and progressed gradually to a moderate-to-severe loss, a pattern generally associated in other, better-characterized dominant progressive sensorineural hearing loss genes with basal (high-frequency-encoding) cochlear injury spreading apically over time. This is pattern-matching drawn from the phenotype alone, not a demonstrated cochlear-cell-biology finding specific to this locus, and no histopathological or model-organism data exist to test it.
sensory perception of sound GO:0007605 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased sensory perception of sound (GO:0007605). GO:0007605 is a biological process from the Gene Ontology. ↓ DECREASED
cochlea UBERON:0001844 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in cochlea (UBERON:0001844). UBERON:0001844 is an anatomical location from the Uberon multi-species anatomy ontology.
Show evidence (1 reference)
PMID:12634859 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"Most affected individuals noticed hearing impairment after their teens with subsequent gradual progression to a moderate-severe loss. There were no obvious vestibular dysfunction and other associated abnormalities."
The clinical natural history is the only evidence available for this node, in the absence of any molecular or cellular data.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Autosomal Dominant Nonsyndromic Hearing Loss 47 Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

2
Progressive Sensorineural Hearing Impairment Auditory HP:0000408 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Progressive sensorineural hearing impairment (HP:0000408), qualified as young adult onset. HP:0000408 is a phenotype from the Human Phenotype Ontology.
Onset: YOUNG ADULT
Show evidence (2 references)
PMID:12634859 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"Most affected individuals noticed hearing impairment after their teens with subsequent gradual progression to a moderate-severe loss. There were no obvious vestibular dysfunction and other associated abnormalities."
Establishes onset timing, progression, severity, and the absence of vestibular or other systemic involvement in the founding family.
PMID:37371710 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"DFNA47 | 9p21-p22 | Unknown | Unknown. | Adulthood (2nd-3rd decade) | Sloping | Progressive | HL is initially limited to high frequencies but progressively involves all frequencies, reaching the moderate-to-severe range by the 5th decade of life"
A second, independent source corroborating onset timing, the sloping audiometric configuration, and progression to moderate-to-severe loss by the 5th decade.
High-Frequency Hearing Impairment Auditory HP:0005101 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is High-frequency hearing impairment (HP:0005101). HP:0005101 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37371710 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"DFNA47 | 9p21-p22 | Unknown | Unknown. | Adulthood (2nd-3rd decade) | Sloping | Progressive | HL is initially limited to high frequencies but progressively involves all frequencies, reaching the moderate-to-severe range by the 5th decade of life"
States the high-frequency-first audiometric configuration that defines the early stage of this locus's hearing loss.
🧬

Genetic Associations

1
DFNA47 locus (9p21-22) -- causal gene not identified
relationship_type: CAUSATIVE
Show evidence (6 references)
PMID:12634859 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"A maximum lod score of 3.14 was obtained with marker D9S157 (at theta=0) after a genome wide search. The study of additional markers allowed us to confirm this region with positive lod scores of 3.58 (at theta=0 from D9S285) and of 3.67 (at theta=0 from D9S162). Recombinants define a region of..."
The founding linkage evidence establishing the 9p21-22 locus and its critical interval.
PMID:12634859 NO_EVIDENCE DIRECT PRIMARY RESULT Human Clinical
"Few known genes map to the region, and those possibly related by function to hearing are being screened for disease-causing mutations."
The founding paper itself had not identified a causal gene at publication; no subsequent report has done so either.
PMID:37371710 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"DFNA47 | 9p21-p22 | Unknown | Unknown. | Adulthood (2nd-3rd decade) | Sloping | Progressive | HL is initially limited to high frequencies but progressively involves all frequencies, reaching the moderate-to-severe range by the 5th decade of life"
A 2023 comprehensive narrative review's own summary table independently reconfirms, two decades after the original mapping, that DFNA47's gene remains unknown, and corroborates the founding family's audiometric natural history from a second source.
+ 3 more references
💊

Medical Actions

3
Hearing Aids and Communication Rehabilitation
Action: hearing rehabilitationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is hearing rehabilitation, annotated with Rehabilitation (NCIT:C15315), qualified as Medical Device Hearing Aid. NCIT:C15315 is a clinical intervention from the NCI Thesaurus. Ontology label: Rehabilitation NCIT:C15315
Platform: Device
Standard amplification and communication rehabilitation as high-frequency loss becomes functionally significant. This is general progressive-sensorineural-hearing-loss management; no DFNA47-specific outcome data exist.
Show evidence (1 reference)
PMID:37371710 SUPPORT INDIRECT REVIEW SYNTHESIS Human Clinical
"A long audiological follow-up is of paramount importance to identify hearing threshold deteriorations early and ensure prompt treatment with hearing aids or cochlear implants."
General standard-of-care management for progressive dominant nonsyndromic sensorineural hearing loss, not a DFNA47-specific outcome study, none of which exists.
Cochlear Implantation
Action: cochlear implantationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is cochlear implantation, annotated with Surgical Procedure (NCIT:C15329), qualified as Medical Device Cochlear Implant. NCIT:C15329 is a clinical intervention from the NCI Thesaurus. Ontology label: Surgical Procedure NCIT:C15329
Platform: Surgery
Standard-of-care intervention once hearing loss reaches severe-to-profound levels and hearing aids are no longer sufficient. This is a general-practice inference for progressive sensorineural hearing loss; no DFNA47-specific implantation outcome has been published.
Show evidence (1 reference)
PMID:37371710 SUPPORT INDIRECT REVIEW SYNTHESIS Human Clinical
"A long audiological follow-up is of paramount importance to identify hearing threshold deteriorations early and ensure prompt treatment with hearing aids or cochlear implants."
General standard-of-care management for progressive dominant nonsyndromic sensorineural hearing loss, not a DFNA47-specific outcome study, none of which exists.
Genetic Counselling
Action: genetic counselingNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is genetic counseling (NCIT:C15240). NCIT:C15240 is a clinical intervention from the NCI Thesaurus. Ontology label: Genetic Counseling NCIT:C15240
Platform: Other
Counsel on the 50% transmission probability from a heterozygous affected parent per pregnancy. Penetrance for this locus is not established in the accessible literature and should not be represented to families as complete or reduced. Because no causal gene is cloned, predictive testing in a new family would rely on linkage/segregation analysis rather than a direct variant test, and is only informative in a sufficiently large, multigenerational pedigree.
Show evidence (1 reference)
PMID:12634859 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"Recombinants define a region of approximately 9 cM flanked by markers D9S268 and D9S942."
The mapped interval that would underlie any linkage-based predictive testing in a new, sufficiently informative pedigree.
🔬

Diagnosis

1
Audiometric and Exclusion-Based Genetic Diagnosis
Because no causal gene is known, there is no positive molecular test for "DFNA47." Diagnosis rests on the clinical/audiometric pattern (autosomal dominant, postlingual, progressive, high-frequency-first bilateral sensorineural hearing loss with no syndromic features), combined with a comprehensive hearing-loss gene panel or exome/genome sequencing to exclude the more than 100 known nonsyndromic deafness genes, and, where a sufficiently large and informative pedigree exists, linkage/segregation analysis to the 9p21-22 interval. A diagnosis of DFNA47 in an isolated case or small family is not currently possible on genetic grounds alone.
Show evidence (2 references)
PMID:37371710 SUPPORT INDIRECT REVIEW SYNTHESIS Human Clinical
"The most effective strategy for the diagnosis of non-syndromic genetic HL is to perform a multi-step approach based on next-generation sequencing technologies and copy number variations assays and a thorough clinical evaluation, including physical examination and audiometric tests."
The general multi-step diagnostic strategy this entry's exclusion-based approach for DFNA47 follows, since no positive single-gene test exists for this locus specifically.
PMID:12634859 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"Few known genes map to the region, and those possibly related by function to hearing are being screened for disease-causing mutations."
Confirms that even candidate-gene screening within the mapped interval had not yielded a causal gene at the time of the founding report.
📊

Prevalence

1
Worldwide, published cases
Cases In Literature Not yet documented
Reported in a single large Italian kindred; no independent family or cohort has been published as linked to the 9p21-22 locus in the two decades since, and no population prevalence or incidence estimate exists.
Show evidence (1 reference)
PMID:12634859 NO_EVIDENCE DIRECT PRIMARY RESULT Human Clinical
"Here we report the mapping of a novel locus for autosomal dominant non-syndromic hearing loss, DFNA47, to chromosome 9p21-22 in a large multigenerational Italian family with progressive hearing impairment."
The founding and, to date, only reported family; no prevalence statistic is claimed by the source, so this item records absence of a denominator rather than a positive prevalence finding.
{ }

Source YAML

click to show
name: Autosomal Dominant Nonsyndromic Hearing Loss 47
category: Mendelian
creation_date: "2026-09-24T00:00:00Z"
synonyms:
- DFNA47
- deafness, autosomal dominant 47
- autosomal dominant nonsyndromic deafness type 47
- autosomal dominant nonsyndromic deafness 47
description: >-
  DFNA47 is a mapped-but-gene-unidentified locus (9p21-22) for autosomal
  dominant, postlingual, progressive, nonsyndromic sensorineural hearing
  loss, reported in a single large Italian kindred in 2003. No causal gene
  has been cloned in the two decades since. This entry is deliberately
  narrow: it records the locus mapping, the clinical/audiometric natural
  history reported in the founding family, and why the candidate gene MYO1A
  is excluded (MYO1A is the gene for a different locus, DFNA48, and its
  disease association has itself since been refuted) rather than attributing
  a molecular mechanism, cell type, or targeted treatment the literature
  does not support.
disease_term:
  preferred_term: autosomal dominant nonsyndromic hearing loss 47
  term:
    id: MONDO:0012090
    label: autosomal dominant nonsyndromic hearing loss 47
parents:
- Autosomal Dominant Nonsyndromic Hearing Loss
inheritance:
- name: Autosomal dominant
  description: >-
    Autosomal dominant, mapped by linkage in the single reported Italian
    kindred. A heterozygous affected parent has a 50% probability of
    transmitting the disease haplotype per pregnancy. Penetrance is not
    stated in the accessible primary report or the 2023 review's summary of
    this locus, so no penetrance claim is made here.
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  evidence:
  - reference: PMID:12634859
    reference_title: "A new locus (DFNA47) for autosomal dominant non-syndromic inherited hearing loss maps to 9p21-22 in a large Italian family."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Here we report the mapping of a novel locus for autosomal dominant non-syndromic hearing loss, DFNA47, to chromosome 9p21-22 in a large multigenerational Italian family with progressive hearing impairment."
    explanation: >-
      Establishes the dominant mode of transmission and the founding
      linkage mapping to the 9p21-22 locus.
    quote_role: PRIMARY_RESULT
    directness: DIRECT
pathophysiology:
- name: Progressive Cochlear Dysfunction at an Unidentified Molecular Target
  description: >-
    No causal gene, transcript, or protein has been identified for DFNA47
    despite the locus having been mapped by linkage analysis in 2003, so no
    molecular pathway, cellular process, or protein-level mechanism can be
    attributed to it. The only mechanistic inference available is drawn from
    the clinical audioprofile itself: hearing loss in the founding family
    began after the teenage years and progressed gradually to a
    moderate-to-severe loss, a pattern generally associated in other,
    better-characterized dominant progressive sensorineural hearing loss
    genes with basal (high-frequency-encoding) cochlear injury spreading
    apically over time. This is pattern-matching drawn from the phenotype
    alone, not a demonstrated cochlear-cell-biology finding specific to this
    locus, and no histopathological or model-organism data exist to test it.
  biological_scale: TISSUE
  locations:
  - preferred_term: cochlea
    term:
      id: UBERON:0001844
      label: cochlea
  biological_processes:
  - preferred_term: sensory perception of sound
    term:
      id: GO:0007605
      label: sensory perception of sound
    modifier: DECREASED
  downstream:
  - target: High-Frequency Hearing Impairment
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      The inferred basal (high-frequency-encoding) cochlear injury is the
      proposed substrate for the early, high-frequency-predominant stage
      of the audioprofile; no intermediate molecular or cellular step has
      been demonstrated for this locus.
  - target: Progressive Sensorineural Hearing Impairment
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      The causal chain from the unidentified 9p21-22 variant to hearing
      loss is entirely inferred; no intermediate molecular or cellular step
      has been demonstrated for this locus.
  evidence:
  - reference: PMID:12634859
    reference_title: "A new locus (DFNA47) for autosomal dominant non-syndromic inherited hearing loss maps to 9p21-22 in a large Italian family."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Most affected individuals noticed hearing impairment after their teens with subsequent gradual progression to a moderate-severe loss. There were no obvious vestibular dysfunction and other associated abnormalities."
    explanation: >-
      The clinical natural history is the only evidence available for this
      node, in the absence of any molecular or cellular data.
    quote_role: PRIMARY_RESULT
    directness: DIRECT
  mechanism_confidence: HYPOTHETICAL
phenotypes:
- name: Progressive Sensorineural Hearing Impairment
  category: Auditory
  description: >-
    Bilateral, postlingual, progressive sensorineural hearing loss, first
    noticed after the teenage years in the founding Italian kindred, with
    gradual progression to a moderate-to-severe loss. No vestibular
    dysfunction or other systemic abnormality is present; hearing is the
    sole affected domain, consistent with a nonsyndromic classification.
  phenotype_term:
    preferred_term: Progressive sensorineural hearing impairment
    term:
      id: HP:0000408
      label: Progressive sensorineural hearing impairment
    onset:
      onset_category: YOUNG_ADULT
      notes: >-
        Reported as noticed "after their teens" in the founding family, with
        subsequent gradual progression; the 2023 review independently
        summarizes DFNA47 onset as "Adulthood (2nd-3rd decade)". No more
        precise age range is given in either source.
  evidence:
  - reference: PMID:12634859
    reference_title: "A new locus (DFNA47) for autosomal dominant non-syndromic inherited hearing loss maps to 9p21-22 in a large Italian family."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Most affected individuals noticed hearing impairment after their teens with subsequent gradual progression to a moderate-severe loss. There were no obvious vestibular dysfunction and other associated abnormalities."
    explanation: >-
      Establishes onset timing, progression, severity, and the absence of
      vestibular or other systemic involvement in the founding family.
    quote_role: PRIMARY_RESULT
    directness: DIRECT
  - reference: PMID:37371710
    reference_title: "Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "DFNA47 | 9p21-p22 | Unknown | Unknown. | Adulthood (2nd-3rd decade) | Sloping | Progressive | HL is initially limited to high frequencies but progressively involves all frequencies, reaching the moderate-to-severe range by the 5th decade of life"
    explanation: >-
      A second, independent source corroborating onset timing, the sloping
      audiometric configuration, and progression to moderate-to-severe
      loss by the 5th decade.
    quote_role: REVIEW_SYNTHESIS
    directness: DIRECT
- name: High-Frequency Hearing Impairment
  category: Auditory
  description: >-
    The defining early audiometric feature of DFNA47: hearing loss is
    initially confined to high frequencies before progressively involving
    all frequencies and reaching a moderate-to-severe pantonal loss by the
    5th decade. This is the audioprofile detail behind the pathophysiology
    node's basal-to-apical cochlear injury inference.
  phenotype_term:
    preferred_term: High-frequency hearing impairment
    term:
      id: HP:0005101
      label: High-frequency hearing impairment
  evidence:
  - reference: PMID:37371710
    reference_title: "Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "DFNA47 | 9p21-p22 | Unknown | Unknown. | Adulthood (2nd-3rd decade) | Sloping | Progressive | HL is initially limited to high frequencies but progressively involves all frequencies, reaching the moderate-to-severe range by the 5th decade of life"
    explanation: >-
      States the high-frequency-first audiometric configuration that
      defines the early stage of this locus's hearing loss.
    quote_role: REVIEW_SYNTHESIS
    directness: DIRECT
genetic:
- name: DFNA47 locus (9p21-22) -- causal gene not identified
  notes: >-
    No causal gene has been cloned for DFNA47 despite the locus having been
    mapped by linkage analysis in 2003 (multipoint LOD 4.26; a critical
    interval of approximately 9 cM flanked by markers D9S268 and D9S942,
    with peak two-point LOD 3.67 at marker D9S162). MYO1A, a
    cochlear-expressed unconventional myosin gene reported in 2003 to carry
    multiple mutations in Italian hearing-loss patients, is NOT the DFNA47
    gene: MYO1A maps to the separate DFNA48 locus (15q22-q25), and its
    proposed association with nonsyndromic deafness has itself since been
    refuted by an independent genotypic-ascertainment study that found no
    bilateral moderate-or-greater sensorineural hearing loss among carriers
    of the implicated MYO1A variants. This entry should not be bound to
    MYO1A. A separate recessive locus, DFNB83, was mapped to 9p23-p21.2 in a
    consanguineous Palestinian family and overlaps the DFNA47 cytogenetic
    band; whether the two represent allelic disorders of one still-uncloned
    gene is an unconfirmed hypothesis based only on the two loci's
    proximity, not a demonstrated fact -- no shared causal variant has been
    published for either locus.
  relationship_type: CAUSATIVE
  evidence:
  - reference: PMID:12634859
    reference_title: "A new locus (DFNA47) for autosomal dominant non-syndromic inherited hearing loss maps to 9p21-22 in a large Italian family."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A maximum lod score of 3.14 was obtained with marker D9S157 (at theta=0) after a genome wide search. The study of additional markers allowed us to confirm this region with positive lod scores of 3.58 (at theta=0 from D9S285) and of 3.67 (at theta=0 from D9S162). Recombinants define a region of approximately 9 cM flanked by markers D9S268 and D9S942. Multipoint linkage analysis showed a Lod score of 4.26."
    explanation: The founding linkage evidence establishing the 9p21-22 locus and its critical interval.
    quote_role: PRIMARY_RESULT
    directness: DIRECT
  - reference: PMID:12634859
    reference_title: "A new locus (DFNA47) for autosomal dominant non-syndromic inherited hearing loss maps to 9p21-22 in a large Italian family."
    supports: NO_EVIDENCE
    evidence_source: HUMAN_CLINICAL
    snippet: "Few known genes map to the region, and those possibly related by function to hearing are being screened for disease-causing mutations."
    explanation: >-
      The founding paper itself had not identified a causal gene at
      publication; no subsequent report has done so either.
    quote_role: PRIMARY_RESULT
    directness: DIRECT
  - reference: PMID:37371710
    reference_title: "Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "DFNA47 | 9p21-p22 | Unknown | Unknown. | Adulthood (2nd-3rd decade) | Sloping | Progressive | HL is initially limited to high frequencies but progressively involves all frequencies, reaching the moderate-to-severe range by the 5th decade of life"
    explanation: >-
      A 2023 comprehensive narrative review's own summary table
      independently reconfirms, two decades after the original mapping,
      that DFNA47's gene remains unknown, and corroborates the founding
      family's audiometric natural history from a second source.
    quote_role: REVIEW_SYNTHESIS
    directness: DIRECT
  - reference: PMID:12736868
    reference_title: "Multiple mutations of MYO1A, a cochlear-expressed gene, in sensorineural hearing loss."
    supports: NO_EVIDENCE
    evidence_source: HUMAN_CLINICAL
    snippet: "MYO1A, which is located within the DFNA48 locus, is the first myosin I family member found to be involved in causing deafness and may be a major contributor to autosomal dominant-hearing loss."
    explanation: >-
      The paper's own text places MYO1A within DFNA48, a different locus
      from DFNA47; cited to document why MYO1A must not be bound as this
      entry's causal gene.
    quote_role: PRIMARY_RESULT
    directness: DIRECT
  - reference: PMID:27759032
    reference_title: "A genotypic ascertainment approach to refute the association of MYO1A variants with non-syndromic deafness."
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: "None of the participants had bilateral sensorineural hearing loss of moderate or greater severity. These data do not support a causal relationship of variants in MYO1A to sensorineural hearing loss."
    explanation: >-
      An independent genotypic-ascertainment study refutes the proposed
      MYO1A-deafness association entirely, reinforcing that MYO1A is not a
      usable candidate gene for any DFNA locus, including DFNA47.
    quote_role: PRIMARY_RESULT
    directness: DIRECT
  - reference: PMID:19888295
    reference_title: "Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families."
    supports: NO_EVIDENCE
    evidence_source: HUMAN_CLINICAL
    snippet: "In six families, we identified five genomic regions likely to harbor novel genes for human hearing loss on chromosomes 1p13.3 (DFNB82), 9p23-p21.2/p13.3-q21.13 (DFNB83), 12q14.3-q21.2 (DFNB84; two families), 14q23.1-q31.1, and 17p12-q11.2 (DFNB85)."
    explanation: >-
      Reports the recessive DFNB83 locus at 9p23-p21.2, cytogenetically
      overlapping the DFNA47 interval; cited only for the locus mapping
      itself. The abstract does not claim allelism with DFNA47, and none is
      asserted here beyond the cytogenetic proximity.
    quote_role: PRIMARY_RESULT
    directness: INDIRECT
diagnosis:
- name: Audiometric and Exclusion-Based Genetic Diagnosis
  description: >-
    Because no causal gene is known, there is no positive molecular test for
    "DFNA47." Diagnosis rests on the clinical/audiometric pattern (autosomal
    dominant, postlingual, progressive, high-frequency-first bilateral
    sensorineural hearing loss with no syndromic features), combined with a
    comprehensive hearing-loss gene panel or exome/genome sequencing to
    exclude the more than 100 known nonsyndromic deafness genes, and, where a
    sufficiently large and informative pedigree exists, linkage/segregation
    analysis to the 9p21-22 interval. A diagnosis of DFNA47 in an isolated
    case or small family is not currently possible on genetic grounds alone.
  evidence:
  - reference: PMID:37371710
    reference_title: "Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most effective strategy for the diagnosis of non-syndromic genetic HL is to perform a multi-step approach based on next-generation sequencing technologies and copy number variations assays and a thorough clinical evaluation, including physical examination and audiometric tests."
    explanation: >-
      The general multi-step diagnostic strategy this entry's
      exclusion-based approach for DFNA47 follows, since no positive
      single-gene test exists for this locus specifically.
    quote_role: REVIEW_SYNTHESIS
    directness: INDIRECT
  - reference: PMID:12634859
    reference_title: "A new locus (DFNA47) for autosomal dominant non-syndromic inherited hearing loss maps to 9p21-22 in a large Italian family."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Few known genes map to the region, and those possibly related by function to hearing are being screened for disease-causing mutations."
    explanation: >-
      Confirms that even candidate-gene screening within the mapped interval
      had not yielded a causal gene at the time of the founding report.
    quote_role: PRIMARY_RESULT
    directness: DIRECT
prevalence:
- population: Worldwide, published cases
  measure_type: CASES_IN_LITERATURE
  prevalence_class: NOT_YET_DOCUMENTED
  notes: >-
    Reported in a single large Italian kindred; no independent family or
    cohort has been published as linked to the 9p21-22 locus in the two
    decades since, and no population prevalence or incidence estimate
    exists.
  evidence:
  - reference: PMID:12634859
    reference_title: "A new locus (DFNA47) for autosomal dominant non-syndromic inherited hearing loss maps to 9p21-22 in a large Italian family."
    supports: NO_EVIDENCE
    evidence_source: HUMAN_CLINICAL
    snippet: "Here we report the mapping of a novel locus for autosomal dominant non-syndromic hearing loss, DFNA47, to chromosome 9p21-22 in a large multigenerational Italian family with progressive hearing impairment."
    explanation: >-
      The founding and, to date, only reported family; no prevalence
      statistic is claimed by the source, so this item records absence of a
      denominator rather than a positive prevalence finding.
    quote_role: PRIMARY_RESULT
    directness: DIRECT
treatments:
- name: Hearing Aids and Communication Rehabilitation
  description: >-
    Standard amplification and communication rehabilitation as
    high-frequency loss becomes functionally significant. This is general
    progressive-sensorineural-hearing-loss management; no DFNA47-specific
    outcome data exist.
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: hearing rehabilitation
    term:
      id: NCIT:C15315
      label: Rehabilitation
    qualifiers:
    - predicate:
        preferred_term: Medical Device
        term:
          id: NCIT:C16830
          label: Medical Device
      value:
        preferred_term: Hearing Aid
        term:
          id: NCIT:C183182
          label: Hearing Aid
  evidence:
  - reference: PMID:37371710
    reference_title: "Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A long audiological follow-up is of paramount importance to identify hearing threshold deteriorations early and ensure prompt treatment with hearing aids or cochlear implants."
    explanation: >-
      General standard-of-care management for progressive dominant
      nonsyndromic sensorineural hearing loss, not a DFNA47-specific
      outcome study, none of which exists.
    quote_role: REVIEW_SYNTHESIS
    directness: INDIRECT
- name: Cochlear Implantation
  description: >-
    Standard-of-care intervention once hearing loss reaches severe-to-profound
    levels and hearing aids are no longer sufficient. This is a
    general-practice inference for progressive sensorineural hearing loss;
    no DFNA47-specific implantation outcome has been published.
  therapeutic_modality: SURGERY
  treatment_term:
    preferred_term: cochlear implantation
    term:
      id: NCIT:C15329
      label: Surgical Procedure
    qualifiers:
    - predicate:
        preferred_term: Medical Device
        term:
          id: NCIT:C16830
          label: Medical Device
      value:
        preferred_term: Cochlear Implant
        term:
          id: NCIT:C157820
          label: Cochlear Implant
  evidence:
  - reference: PMID:37371710
    reference_title: "Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A long audiological follow-up is of paramount importance to identify hearing threshold deteriorations early and ensure prompt treatment with hearing aids or cochlear implants."
    explanation: >-
      General standard-of-care management for progressive dominant
      nonsyndromic sensorineural hearing loss, not a DFNA47-specific
      outcome study, none of which exists.
    quote_role: REVIEW_SYNTHESIS
    directness: INDIRECT
  notes: >-
    No DFNA47-specific implantation case has been reported in the accessible
    literature; included as standard-of-care management for
    severe-to-profound progressive sensorineural hearing loss in general,
    not as a disease-specific finding.
- name: Genetic Counselling
  description: >-
    Counsel on the 50% transmission probability from a heterozygous affected
    parent per pregnancy. Penetrance for this locus is not established in
    the accessible literature and should not be represented to families as
    complete or reduced. Because no causal gene is cloned, predictive
    testing in a new family would rely on linkage/segregation analysis
    rather than a direct variant test, and is only informative in a
    sufficiently large, multigenerational pedigree.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: NCIT:C15240
      label: Genetic Counseling
  evidence:
  - reference: PMID:12634859
    reference_title: "A new locus (DFNA47) for autosomal dominant non-syndromic inherited hearing loss maps to 9p21-22 in a large Italian family."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Recombinants define a region of approximately 9 cM flanked by markers D9S268 and D9S942."
    explanation: >-
      The mapped interval that would underlie any linkage-based predictive
      testing in a new, sufficiently informative pedigree.
    quote_role: PRIMARY_RESULT
    directness: DIRECT
📚

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 (2)

Address review round 1: remove unsourced penetrance claim, add high-frequency phenotype · 2026-09-24T20:15:29Z · View source

Addressed the ai4c-reviewer changes-requested review on PR 12716. Blocking: (1) removed the 'complete penetrance' claim from both the inheritance description and the Genetic Counselling treatment -- re-checked both cached references (PMID:12634859 abstract, PMID:37371710 full text) and confirmed neither states a penetrance figure for this locus specifically; the claim had come from the deep-research report without its own citation, so it was removed rather than re-sourced. (2) Added a second phenotype, High-Frequency Hearing Impairment (HP:0005101), quoting the same PMID:37371710 review table row already used elsewhere in the entry, and wired the pathophysiology node's downstream edges to both phenotypes (previously only Progressive Sensorineural Hearing Impairment was linked). Suggestions taken: dropped the unsourced laterality: BILATERAL field; added a structured onset_category: YOUNG_ADULT backed by a second source (the review's 'Adulthood (2nd-3rd decade)' independently corroborating the founding family's onset timing); added evidence to the previously bare Cochlear Implantation treatment (the same general standard-of-care quote used on Hearing Aids); replaced the weak diagnosis-section evidence quote with the review's own sentence on the multi-step NGS/CNV diagnostic strategy for non-syndromic genetic hearing loss, which more precisely supports the exclusion-based diagnostic approach this entry describes. Re-validated with just validate-disorders (clean, 17/17 snippets and titles) plus check-folded-hyphens, check-duplicate-keys, check-entity-refs, check-causal-targets, check-qualifier-terms.

Create: Autosomal Dominant Nonsyndromic Hearing Loss 47 · 2026-09-24T20:04:55Z · View source

Claimed via issue #12713 and curated from the general dismech curation stub queue. Ran just research-disorder claude_code first (research/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_47-deep-research-claude_code.md), which established that DFNA47 is a mapped-but-gene-unidentified locus (9p21-22, D'Adamo et al. 2003, PMID:12634859): a single large Italian kindred, no independent replication family in the 20+ years since, and no causal gene ever cloned. Critically, the research report flagged that MYO1A -- the gene an agent working from memory might guess, since it is a cochlear-expressed deafness gene from the same era -- is actually the DFNA48 gene (15q22-q25), a different locus, and that MYO1A's own proposed deafness association has itself since been refuted (PMID:27759032). Verified every identifier independently via runoak/PubMed rather than trusting the report: this caught that the report's own PMC-derived citation for the Shahin et al. 2010 DFNB83 paper resolved to the wrong PMID (20602914, an unrelated DFNB82/GPSM2 paper) -- the correct PMID is 19888295. Also corrected UBERON:0001846 (internal ear, too broad) to UBERON:0001844 (cochlea), and CL:0000201 (obsolete) to its replacement CL:0000202 (auditory hair cell), though CL:0000202 was not ultimately used since no cell-type-specific claim is supported for this locus. Given the extreme evidentiary sparsity (no gene, no mechanism beyond phenotype-level pattern-matching, no model organisms, no GeneReviews chapter confirmed via just check-genereviews --online, no disease-specific treatment data), the entry is deliberately narrow: locus mapping and inheritance (from the 2003 founding paper), one phenotype (progressive sensorineural hearing impairment), a genetic entry recording the locus and explicitly why MYO1A is excluded (five evidence items, mixing NO_EVIDENCE/REFUTE grades to document the excluded candidate rather than omitting the reasoning), audiometric/exclusion-based diagnosis, a CASES_IN_LITERATURE prevalence record noting the single-family denominator, and generic standard-of-care treatments (hearing aids, cochlear implantation, genetic counseling) explicitly marked as not DFNA47-specific. Independently corroborated the founding family's audioprofile via a second source, a 2023 DFNA comprehensive review (PMID:37371710) whose own summary table still lists DFNA47's gene as unknown. Validated with just validate-disorders (schema/terms/references clean, 13/13 snippets and titles verified), just check-folded-hyphens, check-duplicate-keys, check-entity-refs, check-causal-targets, and check-qualifier-terms, all clean. Deleted stubs/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_47.yaml.

Claude Code ▸
Autosomal Dominant Nonsyndromic Hearing Loss 47 (DFNA47) — Comprehensive Research Report
claude-haiku-4-5-20251001, claude-sonnet-5 9 citations 2026-09-24T19:53:44.278850

Autosomal Dominant Nonsyndromic Hearing Loss 47 (DFNA47) — Comprehensive Research Report

Executive Summary

DFNA47 (OMIM 608652; MONDO:0012090; ORPHA:90635) is a genetic locus, not yet a gene, for autosomal dominant nonsyndromic (isolated) sensorineural hearing loss. It was mapped by linkage analysis to chromosome 9p21–p22 in a single large multigenerational Italian family by D'Adamo et al. (2003), and the causative gene has never been identified in the more than two decades since — the most recent comprehensive DFNA review (2023) still lists DFNA47 as "unknown gene."¹ This fundamentally shapes what can be reported: sections on genetics, molecular mechanism, biomarkers, targeted treatment, and animal models are necessarily sparse or absent, and that absence is itself the key finding to document faithfully rather than to paper over with inference. Where the source template's search prompts point toward genes such as MYO1A, that gene is in fact linked to a different locus (DFNA48, 15q22-q25), and this report flags that distinction explicitly to avoid the exact kind of cross-locus confusion the dismech ontology-term contract warns against.


1. Disease Information

Overview. DFNA47 is an autosomal dominant, postlingual, progressive, nonsyndromic (isolated) sensorineural hearing loss (SNHL). It was described in a single large Italian kindred; affected individuals have no other associated abnormalities — hearing loss is the sole phenotype, with no vestibular, ophthalmologic, renal, or other systemic involvement reported.¹²

Key identifiers:

Resource Identifier
OMIM (phenotype) 608652 — DEAFNESS, AUTOSOMAL DOMINANT 47; DFNA47 (a locus-designation "number sign"-less entry, denoting a mapped-but-gene-unknown phenotype)²
MONDO MONDO:0012090
Orphanet ORPHA:90635
Gene Symbol Not established — no causal gene has been cloned
Cytogenetic locus 9p21–p22 (also cited as 9p22-p21)
Physical interval (GRCh37/hg19, per Shahin et al. 2010) approximately chr9:13,046,167–21,980,675
ICD-10 H90.5 (Unspecified sensorineural hearing loss) or H90.3 (Bilateral sensorineural hearing loss) — no DFNA47-specific code exists
MeSH D003638 (Deafness) / D006319 (Hearing Loss, Sensorineural) — no locus-specific term

Synonyms/alternative names: DEAFNESS, AUTOSOMAL DOMINANT 47; DFNA47 locus; progressive postlingual autosomal dominant nonsyndromic hearing loss (9p21-p22-linked).

Source of information: All disease-level knowledge derives from aggregated, published pedigree/linkage data, not individual-patient EHR data — specifically one extended Italian family reported in a single primary linkage paper (D'Adamo et al., 2003), subsequently catalogued in locus databases (OMIM, Hereditary Hearing Loss Homepage, Orphanet) and cited in review literature. No subsequent independent family or cohort has been reported as linked to this locus, so the evidentiary base is unusually narrow — essentially n = 1 family.


2. Etiology

Disease causal factor: Purely genetic — an autosomal dominant mendelian trait mapped to 9p21–p22 with complete penetrance in the reported family. The causal gene/variant is unknown.

Genetic risk factors: - Inheriting the disease haplotype at the 9p21-p22 DFNA47 interval from an affected parent (autosomal dominant, one copy sufficient). - No specific pathogenic variant, susceptibility allele, or modifier locus has been published, because the gene itself has not been cloned. - Possible allelism with DFNB83 (a recessive nonsyndromic hearing-loss locus): Shahin et al. (2010) mapped DFNB83 to a 16.5-Mb interval on 9p23–p21.2 in a consanguineous Palestinian family and noted this interval encompasses the DFNA47 region, raising the hypothesis that different mutation types (loss-of-function vs. dominant-negative/gain-of-function) in the same still-unidentified gene could underlie both the recessive (DFNB83) and dominant (DFNA47) phenotypes.³ This is a genotype-driven allelic-series hypothesis, not a confirmed finding — the gene for DFNB83 has also not been definitively cloned in the public literature reviewed here.

Environmental risk factors: None reported or plausible as a primary cause — this is described as a fully penetrant monogenic trait. No published data associate noise exposure, ototoxic drugs, or other environmental modifiers with age of onset or severity in this specific family.

Protective factors: None reported (genetic or environmental) — not applicable given the small literature.

Gene-environment interactions: Not studied for DFNA47 specifically; no data available.


3. Phenotypes

The sole phenotype domain affected is hearing — DFNA47 is explicitly nonsyndromic. The original description (D'Adamo et al., 2003) and subsequent OMIM/review synopses converge on:

Phenotype Type HPO term (suggested) Onset Severity/progression Frequency in family
Progressive sensorineural hearing loss Clinical sign/symptom HP:0000407 Sensorineural hearing impairment Audiometric abnormality detectable age 20–25 yr; subjectively noticed age 30–35 yr Progressive: initially high-frequency, later spreading to mid/low frequencies; moderate-to-severe by ~age 50 Fully penetrant in affected branches of the pedigree
High-frequency-predominant hearing loss (early stage) Audiometric configuration HP:0000407 (general) / audiometric "sloping/downsloping" configuration is a clinical descriptor, not a distinct HPO term 2nd–3rd decade Mild-to-moderate initially —
Postlingual onset (language already acquired before hearing loss) Temporal qualifier HP:0000403-adjacent concept (postlingual onset is typically captured via onset-age slots rather than a dedicated HPO term) By definition, after speech acquisition — —
Absence of vestibular dysfunction Negative finding (Absence of HP:0000737 Vestibular dysfunction) N/A Not present Explicitly noted as absent in the reported family

Characteristics: - Age of onset: Adult-onset (2nd–3rd decade for audiometric detection; symptomatic recognition somewhat later, 3rd–4th decade). - Severity: Variable but consistently progressive — mild/high-frequency-only in young adulthood, evolving to moderate-to-severe pantonal loss by the 5th decade. - Progression: Progressive (not stable, not episodic) — a classic "sloping-worsening-to-flat" audiometric trajectory over decades. - Frequency among affected individuals: Fully penetrant — every gene-carrier in the reported pedigree was reported as eventually affected (penetrance described as complete, distinguishing it from many other DFNA loci with age-dependent incomplete penetrance).

Quality-of-life impact: Not formally measured in the primary literature (no EQ-5D, SF-36, or hearing-specific QoL instrument data published for this specific cohort). By inference from the general adult-onset progressive SNHL literature, such presentations are associated with progressive communication difficulty, and — because onset is postlingual and gradual — patients typically retain spoken language but experience increasing functional impairment (speech-in-noise difficulty, social withdrawal risk) as the loss becomes moderate-to-severe in the 5th decade. No disease-specific QoL study exists.

No other organ systems, syndromic features, developmental abnormalities, or laboratory abnormalities have been reported.


4. Genetic/Molecular Information

This section is the most constrained by the state of the science.

  • Causal gene: Unidentified. No gene has been cloned, validated, or widely accepted as the DFNA47 gene despite the locus having been mapped in 2003. The 2023 comprehensive DFNA review (PMC10296186) explicitly lists the gene status for DFNA47 as "Unknown gene."¹
  • Locus/candidate interval: 9p21–p22; narrowed by recombinant analysis in the original family to an approximately 9-cM interval between microsatellite markers D9S268 and D9S942, with peak linkage (LOD = 3.67 at θ = 0.0) at marker D9S162.⁴
  • Overlapping recessive locus: DFNB83 (OMIM 613685), mapped by Shahin et al. (2010) to a 16.5-Mb region on 9p23–p21.2 (LOD = 3.07, markers rs4742645–rs1471364) in a consanguineous Palestinian family, is reported to physically encompass the DFNA47 interval (~chr9:13,046,167–21,980,675), suggesting the two loci may represent allelic disorders of one still-uncloned gene.³ This remains a hypothesis, not a demonstrated fact — no shared causal variant has been published.
  • Pathogenic variants: None reported — there is no ClinVar, HGMD, or gnomAD entry attributable to "the DFNA47 gene" because no such gene designation exists in variant databases.
  • A note on MYO1A (flagged specifically because the research-template's search prompts for this section would otherwise lead a curator toward it): MYO1A, a cochlear-expressed unconventional myosin gene, was reported by Donaudy et al. (2003, PMID:12736868) to carry multiple mutations (one nonsense, one in-frame trinucleotide insertion, six missense) in Italian patients with moderate-to-severe (never profound) bilateral SNHL.⁵ However, MYO1A maps to chromosome 15q22-q25 and is associated with locus DFNA48, not DFNA47 — the two loci are numerically adjacent but genetically and cytogenetically distinct. Furthermore, the MYO1A-deafness association itself has since been substantially refuted: a 2016 genotypic-ascertainment study (Eisenberger et al./Lee et al., PMID:27759032, Eur J Hum Genet) found the originally reported MYO1A variants also present in unaffected controls and in individuals whose hearing loss was better explained by pathogenic variants in other, well-established deafness genes, concluding MYO1A variants are not a convincing cause of nonsyndromic deafness.⁶ DFNA47 curators should not bind this entry's causal gene to MYO1A — that would conflate two different OMIM loci and cite evidence for a claim now considered unsupported in the literature.
  • Modifier genes, epigenetics, chromosomal abnormalities: No data published for DFNA47.
  • Functional consequences: Cannot be characterized (variant type, LOF vs. GOF, dominant-negative mechanism) because no variant has been identified.

Suggested ontology bindings for the locus/phenotype layer (not gene layer, since none exists): - Phenotype: HP:0000407 (Sensorineural hearing impairment) - Mode of inheritance: HP:0000006 (Autosomal dominant inheritance) - Onset: HP:0011462 (Young adult onset) or HP:0003621 (Juvenile onset) depending on how audiometric-vs-symptomatic onset ages are modeled


5. Environmental Information

No environmental factors, lifestyle factors, or infectious agents have been reported as contributing to or modifying DFNA47. As a fully penetrant monogenic trait in the single reported family, environmental influence on penetrance/expressivity was not a subject of the original study and has not been investigated since. Not applicable / no data.


6. Mechanism / Pathophysiology

Causal chain (as currently understood — heavily inferred, since the gene is unknown):

  1. An as-yet-unidentified dominant pathogenic variant at the 9p21–p22 locus is inherited (autosomal dominant, fully penetrant) → [inferred, not demonstrated]
  2. The variant is presumed to disrupt a gene product expressed in, or required for maintenance of, cochlear sensory or supporting cells (by analogy to essentially all other cloned DFNA genes, which encode structural, motor, ion-channel, or transcriptional proteins active in the organ of Corti, stria vascularis, or spiral ganglion) → [inferred by analogy; no direct evidence for DFNA47 specifically]
  3. Progressive cochlear dysfunction develops with age, beginning in the basal (high-frequency-encoding) turn of the cochlea — consistent with the clinical audioprofile of initial high-frequency loss — and spreading apically over decades to involve mid- and low-frequency hearing → [clinically observed, mechanistically unexplained]
  4. This manifests as postlingual, progressive sensorineural hearing loss reaching moderate-to-severe severity by the 5th decade, with the vestibular end-organ spared (no reported vestibular dysfunction), implying any underlying cellular process is either cochlea-restricted or has a threshold effect not reached in the vestibular system → [clinical observation]

Because no gene, transcript, or protein has been identified, none of the following can be populated with disease-specific data: - Molecular pathways (no KEGG/Reactome pathway can be assigned to an unknown gene) - Cellular processes / GO biological process terms - Protein structure/dysfunction (misfolding, LOF, GOF, dominant-negative) - Metabolic changes - Immune involvement (none expected/reported for a nonsyndromic SNHL locus) - Tissue damage mechanisms at the molecular level - Biochemical abnormalities - Epigenetic changes - Any -omics profiling (transcriptomic, proteomic, metabolomic, lipidomic, single-cell, spatial) — no such studies exist for this locus, since there is no gene or model system to study - Functional genomic screens

The only mechanistic inference that can be responsibly drawn from the clinical phenotype alone is the general pattern typical of progressive DFNA loci: a high-frequency-first, base-to-apex progression consistent with basal cochlear outer/inner hair cell vulnerability, by analogy with better-characterized dominant progressive SNHL genes (e.g., TECTA, COCH, WFS1), but this is pattern-matching, not evidence specific to DFNA47, and should not be curated as a mechanistic claim without an explicit caveat.

Suggested ontology terms for a maximally conservative (phenotype-level only) pathophysiology annotation: - UBERON:0001846 (cochlea) as the presumed affected structure - GO:0007605 (sensory perception of sound) as the disrupted process at the organismal level - CL:0000201 (auditory hair cell) — candidate cell type by analogy to other DFNA loci, but unconfirmed for this specific locus


7. Anatomical Structures Affected

  • Organ level: Primary organ affected — the inner ear (cochlea); specifically the auditory portion (organ of Corti). Secondary organ involvement: none reported. Body system: auditory/special sensory system only (nonsyndromic).
  • Tissue/cell level: Presumed cochlear sensory epithelium (hair cells) and/or supporting structures (stria vascularis, spiral ligament, spiral ganglion), by analogy with other progressive DFNA phenotypes — not directly demonstrated for DFNA47, since no histopathology, temporal bone study, or animal model exists for this locus.
  • Suggested CL term (candidate, unconfirmed): CL:0000201 (auditory hair cell)
  • Subcellular level: Cannot be specified — no molecular target known.
  • Localization: Bilateral (both cochleae affected symmetrically, consistent with a germline dominant trait); UBERON:0001846 (cochlea). No lateralization/asymmetry reported.

8. Temporal Development

  • Onset: Adult-onset — audiometric threshold changes first detectable around age 20–25 years; subjective symptom awareness around age 30–35 years. Onset pattern is insidious/gradual, not acute.
  • Progression: Slowly progressive over decades. Disease "stages" are not formally defined (no published staging system specific to DFNA47), but the natural history can be summarized as three informal phases:
  • Subclinical/early audiometric — high-frequency threshold elevation, 2nd–3rd decade, often asymptomatic
  • Symptomatic progressive — 4th decade, expanding to mid frequencies, noticeable functional impact
  • Established moderate-to-severe pantonal loss — by the 5th decade (~age 50)
  • Disease course pattern: Progressive, not relapsing-remitting or episodic. Lifelong/chronic — no spontaneous remission reported.
  • Critical periods: None identified; because onset is postlingual, spoken language acquisition is not at risk, distinguishing DFNA47 clinically from prelingual/congenital deafness loci where early intervention windows are critical.

9. Inheritance and Population

  • Epidemiology: No population-level prevalence or incidence estimate exists. DFNA47 has been reported in essentially one large Italian family; it has not been shown to be a recurrent or population-relevant cause of hearing loss elsewhere, and no locus-specific frequency data appear in Orphanet, GBD, or national registries. Reasonable to classify as ultra-rare (single-family report), but this is a qualitative judgment rather than a sourced numeric estimate.
  • Inheritance pattern: Autosomal dominant (HP:0000006).
  • Penetrance: Reported as complete/fully penetrant in the index family — an unusual and notable feature relative to many other adult-onset DFNA loci, which more commonly show age-dependent, incomplete penetrance.
  • Expressivity: Variable age of onset within the fully penetrant pedigree (audiometric onset 20–25 yr vs. subjective onset 30–35 yr) suggests some variable expressivity in timing, though ultimate severity (moderate-to-severe by age 50) appears consistent across affected members.
  • Genetic anticipation: Not reported/assessed.
  • Germline mosaicism: Not reported.
  • Founder effect: Plausibly relevant, given the single-family, geographically restricted (central/southern Italy region, per the original cohort's ascertainment) origin, but no explicit founder-haplotype study has been published for DFNA47 specifically.
  • Consanguinity: Not a factor — dominant trait, and the original family was ascertained through multigenerational dominant transmission, not consanguinity (contrast with the recessive DFNB83 family, which was consanguineous).
  • Carrier frequency: Not applicable in the classic sense for a dominant, fully penetrant trait with unknown gene (no population carrier-frequency data exist).
  • Population demographics: Only known affected population is the original Italian kindred; no data on other ethnic groups, geographic distribution of the (unknown) variant, sex ratio, or age distribution beyond what is captured in the onset/progression data above.

10. Diagnostics

  • Clinical tests:
  • Pure-tone audiometry is the primary diagnostic tool, demonstrating the characteristic high-frequency-initial, progressively pantonal, sloping-to-flat sensorineural configuration.
  • No disease-specific biomarker, imaging finding, or histopathological signature has been published.
  • Vestibular testing has been reported as normal in affected individuals (used to support the "nonsyndromic, cochlea-restricted" classification).
  • Genetic testing: Because no causal gene is known, there is no commercially or clinically available single-gene or targeted test for "DFNA47." Diagnosis in a new family suspected of DFNA47-type presentation would in practice proceed via:
  • Comprehensive hearing-loss gene panel or clinical exome/genome sequencing (to identify pathogenic variants in the ~150+ known nonsyndromic deafness genes) — used to exclude known genes;
  • Linkage/segregation analysis to the 9p21-p22 interval only if a large, informative, multigenerational pedigree is available — impractical for isolated cases or small families;
  • A diagnosis of "DFNA47" today would essentially be a diagnosis of exclusion plus locus-consistent linkage evidence, not a positive molecular diagnostic result.
  • GTR (Genetic Testing Registry) does not list a validated single-gene assay for this locus, consistent with the absence of a cloned gene.
  • Omics-based diagnostics: Not applicable — no validated RNA-seq, proteomic, or liquid-biopsy diagnostic exists or would be expected for a nonsyndromic nuclear nervous-system-sparing trait.
  • Clinical criteria: No formal consensus diagnostic criteria specific to DFNA47 exist; diagnosis rests on (a) clinical pattern (autosomal dominant, postlingual, progressive, high-frequency-first bilateral SNHL, no syndromic features), (b) exclusion of known deafness genes, and, ideally, (c) demonstration of linkage to 9p21-p22 in a sufficiently large pedigree.
  • Differential diagnosis: Broad — essentially all other progressive autosomal dominant nonsyndromic hearing-loss loci with adult onset and high-frequency-first audioprofiles (e.g., DFNA2/KCNQ4, DFNA8/12/TECTA, DFNA9/COCH, DFNA10/EYA4, DFNA20/26/ACTG1, DFNA48/MYO1A-associated phenotype) must be excluded by molecular testing, since audioprofile alone cannot distinguish DFNA47 from these better-characterized entities.
  • Screening: No newborn or population screening applicable — this is adult-onset, and there is no test to screen for it specifically. Standard newborn hearing screening protocols (which target congenital/early-onset hearing loss) would not detect DFNA47, consistent with its postlingual onset.

11. Outcome/Prognosis

  • Survival/mortality: Not a life-limiting condition; no mortality data relevant (isolated SNHL does not affect survival).
  • Morbidity/function: Progressive functional hearing impairment; by the 5th decade, moderate-to-severe bilateral SNHL is expected in all penetrant carriers, with attendant communication difficulty. No formalized disability outcome or QoL instrument data published for this specific locus.
  • Disease course: No complications beyond the hearing impairment itself have been reported (nonsyndromic — no cardiac, renal, ophthalmologic, or neurologic sequelae). No spontaneous recovery is described or expected, consistent with a progressive sensorineural (rather than conductive/reversible) process.
  • Prognostic factors: The main "prognostic" information available is the pedigree-derived natural history itself (age-linked severity milestones, above) rather than any biomarker-based prognostic model.
  • Prognostic biomarkers: None identified.

12. Treatment

There is no disease-specific (mechanism-targeted) treatment for DFNA47, because there is no known molecular target. Management is the standard supportive/rehabilitative approach used for any progressive sensorineural hearing loss:

  • Pharmacotherapy: None specific; no drug is indicated for the underlying cause. (NCIT: not applicable for a causal pharmacotherapy; general audiologic pharmacotherapy is not disease-modifying here.)
  • Advanced therapeutics:
  • Gene therapy: none developed or in trials for DFNA47 specifically (impossible without a known target gene). General inner-ear gene-therapy platforms under investigation for other, gene-defined SNHL forms (e.g., OTOF-related deafness) are not applicable here.
  • Cell therapy, RNA-based therapy, targeted/immunotherapy: not applicable — no molecular target exists.
  • Surgical/interventional: Cochlear implantation (NCIT:C15329, Surgical Procedure, as the general clinical-action binding; the device itself, NCIT:C157820 Cochlear Implant, would be recorded as a qualifiers device annotation per this repository's convention) would be the expected intervention once hearing loss becomes severe-to-profound and hearing aids are no longer sufficient — this is a standard-of-care inference for progressive SNHL generally, not a DFNA47-specific outcome study.
  • Supportive/rehabilitative:
  • Hearing aid amplification (NCIT:C — no precise device-class NCIT term for "hearing aid" is available in this repository's ontology per the MAXO-removal note; would require a qualifiers device pattern analogous to cochlear implants) is the standard first-line intervention as the high-frequency loss becomes functionally significant.
  • Audiologic rehabilitation / speech-in-noise strategies, aural rehabilitation (NCIT:C15302 Physical Therapy is not a precise fit; NCIT:C159273 Speech-Language Therapy or general "Rehabilitation," NCIT:C15315, would be the closer generic binding for auditory rehabilitation counseling).
  • Experimental: No DFNA47-specific clinical trials identified on ClinicalTrials.gov or WHO ICTRP.
  • Treatment outcomes: No disease-specific data on hearing-aid or cochlear-implant outcomes in DFNA47 carriers (as distinct from general adult-onset progressive SNHL populations) have been published.
  • Treatment strategy / personalized medicine: Not applicable — genotype-guided treatment is impossible without a known gene.

13. Prevention

  • Primary prevention: Not possible for a fully penetrant monogenic trait once inherited; no risk-factor modification applies (no environmental cause identified).
  • Secondary prevention (early detection): Periodic audiometric monitoring of at-risk relatives (known carriers or first-degree relatives of affected individuals in the index pedigree) beginning in the 2nd decade would be a reasonable clinical recommendation by analogy with other adult-onset progressive DFNA loci, allowing earlier initiation of amplification — but this is inferred general practice, not a published DFNA47-specific screening protocol.
  • Tertiary prevention: Early hearing-aid fitting once threshold changes are detected, to minimize functional/communicative impact and reduce risk of auditory deprivation effects.
  • Immunization: Not applicable (not an infectious or immune-mediated condition).
  • Genetic screening: Because no gene is cloned, no targeted prenatal, carrier, or preimplantation genetic test exists for DFNA47. In a family with established linkage, haplotype-based predictive testing (linked-marker segregation analysis) is theoretically possible but has not been reported as clinically implemented, and would require careful genetic counseling given its indirect (linkage-based, not variant-based) nature.
  • Genetic counseling: Standard autosomal dominant counseling principles apply — 50% transmission risk to offspring of an affected individual, complete penetrance implying essentially all gene-carriers will eventually be affected (unlike many incompletely penetrant DFNA loci).
  • Public health / environmental interventions: Not applicable — no environmental contributor identified.
  • Prophylaxis: None available.

14. Other Species / Natural Disease

No orthologous gene can be discussed because the human gene itself is unknown. Consequently:

  • Taxonomy: Not applicable (no gene to compare across species; NCBITaxon:9606 Homo sapiens is the only relevant taxon for this entry).
  • Breed: No naturally occurring veterinary correlate has been linked to this human locus.
  • Orthologous gene: Cannot be identified.
  • Natural disease in other species: No OMIA (Online Mendelian Inheritance in Animals) entry corresponds to DFNA47, since OMIA cross-references are built from known human genes.
  • Comparative biology / evolutionary conservation: Not assessable.
  • Zoonotic potential / cross-species susceptibility: Not applicable (non-infectious, monogenic human trait).

15. Model Organisms

No model organism (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell line, organoid, or iPSC-derived system) has been developed or reported for DFNA47, and none can be rationally engineered until the causal gene is identified — knockout, knock-in, transgenic, or humanized models all require a known target locus/gene. This is a direct and important consequence of the "gene unknown" status and should not be filled in by extrapolating from the retracted MYO1A literature or from other, unrelated DFNA loci's mouse models, since doing so would misattribute model evidence to this specific locus.


Summary: What Can and Cannot Be Curated

Category Status
Locus, mapping, LOD score, markers Well-documented (single primary source)
Clinical/audiometric phenotype, natural history Well-documented (single primary source)
Causal gene Unknown — do not bind to MYO1A (that is DFNA48)
Molecular mechanism, pathway, cell biology Not available — any pathophysiology entry must be built at the phenotype/anatomical level only, explicitly flagged as inferred-by-analogy where used
Genetic testing / variant classification Not available as a positive test; diagnosis is exclusion-based
Treatment Generic SNHL management only (hearing aids, cochlear implantation) — no disease-modifying or targeted therapy
Model organisms None exist
Epidemiology Single-family report only; no population prevalence/incidence figure is sourced

References (with PMIDs where available)

  1. Comprehensive narrative review of autosomal dominant nonsyndromic hearing loss (DFNA), including summary table listing DFNA47 as 9p21–p22, gene unknown, adulthood (2nd–3rd decade) onset, sloping/progressive audioprofile reaching moderate-to-severe by the 5th decade. PMC10296186. https://pmc.ncbi.nlm.nih.gov/articles/PMC10296186/
  2. OMIM Entry 608652 — DEAFNESS, AUTOSOMAL DOMINANT 47; DFNA47. https://omim.org/entry/608652
  3. Shahin H, et al. (2010). Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families. Eur J Hum Genet. — reports DFNB83 (9p23-p21.2) overlapping the DFNA47 interval and proposes possible allelism. PMC2987250. https://pmc.ncbi.nlm.nih.gov/articles/PMC2987250/ ; OMIM DFNB83 entry 613685. https://omim.org/entry/613685
  4. D'Adamo P, et al. (2003). A new locus (DFNA47) for autosomal dominant non-syndromic inherited hearing loss maps to 9p21-22 in a large Italian family. Eur J Hum Genet. PMID:12634859. https://pubmed.ncbi.nlm.nih.gov/12634859/ ; https://www.nature.com/articles/5200929
  5. Donaudy F, et al. (2003). Multiple mutations of MYO1A, a cochlear-expressed gene, in sensorineural hearing loss. Am J Hum Genet. PMID:12736868 — describes the DFNA48-associated gene MYO1A (15q22-q25); distinct from DFNA47. PMC1180318. https://pmc.ncbi.nlm.nih.gov/articles/PMC1180318/
  6. Genotypic ascertainment study refuting the association of MYO1A variants with nonsyndromic deafness. PMID:27759032. Eur J Hum Genet. https://www.nature.com/articles/ejhg2016140 ; https://pmc.ncbi.nlm.nih.gov/articles/PMC5159773/

Note on evidentiary limits

This report is transparent that DFNA47 is among the sparsest entries in the nonsyndromic hearing-loss nosology: essentially one primary linkage paper (2003), one secondary paper noting a possible overlapping recessive locus (2010), and citation in periodic review articles — with no gene-level, mechanistic, diagnostic-test, treatment-specific, or model-organism literature existing at all. Any dismech curation of this entry should reflect that honestly (an entry that is mostly locus/phenotype metadata with notes: explaining the absent gene, rather than an entry padded with inferred or cross-locus content) rather than manufacturing specificity — consistent with this repository's Ontology Term Contract's instruction to omit a field and record why, rather than fabricate a binding, when a claim cannot be sourced.

Reference Validation

Checked with linkml-reference-validator 0.3.0rc1.

Outcome Count
References checked 7
Resolved 7
Unresolved (possible confabulation) 0
Unverifiable 0
References weighed for topical relevance 7
On topic 7
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 17
Resolved 15
Unresolved (possible confabulation) 0
Obsolete 1
Unverifiable 1
Terms whose name was checked 3
Terms named correctly 0
Terms named as a different term 3

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:

  • MONDO:0012090 (2 mentions) - the report calls it "MONDO"; MONDO calls it autosomal dominant nonsyndromic hearing loss 47
  • UBERON:0001846 (2 mentions) - the report calls it "cochlea"; UBERON calls it internal ear
  • CL:0000201 (2 mentions) - the report calls it "auditory hair cell"; CL calls it CL_0000201

Obsolete terms

These terms are real but deprecated. Citing one is not a fabrication; it does mean the report is naming something the ontology has retired:

  • CL:0000201 (CL_0000201) (2 mentions) - replaced by CL:0000202

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: ORPHA.