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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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
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.
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.
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.
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.
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.
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.
This section is the most constrained by the state of the science.
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.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
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.
Causal chain (as currently understood — heavily inferred, since the gene is unknown):
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
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:
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.qualifiers device pattern analogous to cochlear implants) is the standard first-line intervention as the high-frequency loss becomes functionally significant.No orthologous gene can be discussed because the human gene itself is unknown. Consequently:
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.
| 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 |
608652 — DEAFNESS, AUTOSOMAL DOMINANT 47; DFNA47. https://omim.org/entry/608652613685. https://omim.org/entry/613685This 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.
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.
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 |
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 47UBERON:0001846 (2 mentions) - the report calls it "cochlea"; UBERON calls it internal earCL:0000201 (2 mentions) - the report calls it "auditory hair cell"; CL calls it CL_0000201These 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:0000202Terms 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.