Autosomal Dominant Nonsyndromic Hearing Loss 53

Mendelian MONDO:0012380 Pathograph 4 Show in embeddings browser Autosomal Dominant Nonsyndromic Hearing Loss

DFNA53 is a linkage-defined form of autosomal dominant nonsyndromic hearing loss mapped to 14q11.2-q12 in a six-generation family from northern China. Sixteen of 48 genotyped relatives were classified as affected. Hearing loss was bilateral, postlingual and progressive, usually beginning in the second decade, with substantial variability in severity and audiogram shape. Distortion product otoacoustic emissions demonstrated cochlear dysfunction, and caloric responses were normal in the six affected relatives tested. The causal gene and variant remain unidentified in the reviewed sources; the 2023 DFNA review lists both gene and protein function as unknown. Coding-region and splice-boundary screening of four candidate genes did not identify the cause.

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1
Inheritance
2
Pathophys.
2
Phenotypes
1
Gaps
4
Pathograph
1
Genes
5
Medical Actions
3
Differentials
4
References
1
Deep Research
👪

Inheritance

1
Autosomal dominant HP:0000006
Hearing loss segregated as an autosomal dominant trait in three testable generations of a six-generation pedigree. The linkage analysis assumed 90% penetrance in heterozygotes; this was not a measured penetrance estimate. Under a heterozygous dominant model, each child has a 50% chance of inheriting the allele, which is distinct from the age-dependent chance of manifesting hearing loss. No causal variant has been established for variant-specific predictive testing.
Autosomal dominant inheritance
Show evidence (2 references)
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"The clinical history and audiological finding of the hearing loss in family members clearly revealed an autosomal dominant form of post‐lingual, bilateral sensorineural hearing loss."
States the mode of inheritance and the character of the hearing loss in the only reported family.
url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader SUPPORT REVIEW SYNTHESIS Human Clinical
"Individuals with autosomal dominant hearing loss have a 50% chance of transmitting the pathogenic variant to each child."
General autosomal dominant allele-transmission probability; this does not measure DFNA53 clinical penetrance.
?

Discussions and Knowledge Gaps

1
Which causal variant and gene account for the hearing-loss linkage at 14q11.2-q12, and can independent families replicate the association?
KNOWLEDGE GAP OPEN dfna53_causal_gene_unidentified
Attached to
pathophysiology#Unidentified Dominant Allele in the 14q11.2-q12 Interval genetic#DFNA53 locus at 14q11.2-q12
The mapping study provides strong linkage evidence within one pedigree but does not resolve a gene or molecular mechanism. Its coding-region candidate screen left structural and regulatory variation incompletely assessed. Genome analysis could revisit these possibilities if appropriate samples are available, but sample availability is not established by the historical report.
Proposed experiments
Genome sequencing of the original DFNA53 pedigree
dfna53_genome_sequencing_of_the_original_pedigree
If samples and consent are available, sequence affected and informative unaffected relatives using genome methods that assess sequence and structural variation, then evaluate candidates within a remapped D14S581–D14S1021 interval. Account for age-dependent phenotype classification and assay coverage, and seek independent genetic and functional evidence.
Would support
pathophysiology#Unidentified Dominant Allele in the 14q11.2-q12 Interval
Supporting outcome
  • A rare segregating variant would nominate a candidate; replication and functional evidence consistent with the clinical phenotype would strengthen causal attribution.
Refuting outcome
  • Reliable segregation incompatible with the interval or stronger evidence for a different cause would weaken the original locus assignment. Failure to detect a variant alone would remain inconclusive because of assay and interpretation limits.
⚙

Pathophysiology

2
Unidentified Dominant Allele in the 14q11.2-q12 Interval
Mechanism confidence: Provisional
Linkage and recombinant haplotype analysis mapped DFNA53 between D14S581 and D14S1021, a 9.6 cM interval at 14q11.2-q12. The original assembly placed approximately 6.4 Mb and 60 known genes in this interval. A maximum multipoint LOD score of 5.4 supports linkage in the reported pedigree, but the causal gene, variant and molecular mechanism remain unresolved.
Downstream
Cochlear Dysfunction Linkage to the interval and cochlear dysfunction were observed in the same family; the intervening molecular and cellular events are unknown.
Show evidence (2 references)
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"This analysis placed the DFNA53 locus between the proximal marker D14S581 and the distal marker D14S1021, which defines a critical interval of 9.6 cM"
Defines the interval that this node names.
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"This interval spans a physical distance of about 6.4 Mb, and includes ∼60 known genes and a series of predicted or poorly characterised genes"
Historical physical span and gene count reported in the mapping study; not a current genome-assembly coordinate definition.
Cochlear Dysfunction
Distortion product otoacoustic emission testing showed cochlear dysfunction in the affected relatives. Air- and bone-conduction audiometry and oto-immittance were used to assess the sensorineural character of the hearing loss. These findings support cochlear involvement but do not identify a particular cellular lesion or exclude all coexisting retrocochlear dysfunction.
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.
Downstream
Postlingual Progressive Sensorineural Hearing Loss The cochlear lesion is what the audiometric phenotype measures.
High-Frequency Hearing Loss Progressing to All Frequencies The frequency pattern of a progressive cochlear lesion, beginning at the high frequencies and extending downward.
Show evidence (2 references)
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"Distortion product otoacoustic emission (DPOAE) testing in all the affected individuals, using the IL096 DP analyser (Otodynamics UK 1996), showed cochlear dysfunction."
The direct observation this node records.
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"Bone conduction thresholds were determined to exclude a conductive component in patients with hearing loss."
The study assessed bone-conduction thresholds to evaluate a possible conductive component; this is a diagnostic method, not direct molecular evidence.
⬡

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 53 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
Postlingual Progressive Sensorineural Hearing Loss Ear HP:0008596 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Postlingual progressive sensorineural hearing impairment, annotated with Postlingual sensorineural hearing impairment (HP:0008596), qualified as laterality bilateral; course progressive. HP:0008596 is a phenotype from the Human Phenotype Ontology.
Laterality: BILATERAL Course: PROGRESSIVE
Show evidence (3 references)
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"The reported onset of hearing problems in most cases was in the second decade of life with subsequent gradual progression from mild to profound hearing loss involving the high frequencies in the majority of patients."
Onset, severity range and progression in the only reported family.
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"The earliest clinical evidence of hearing loss in the family was obtained from individuals V‐82 and V‐91 at the age of 14 years."
The youngest documented age at onset, which is what a paediatric assessment turns on.
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"Of the 48 individuals in whom DNA was obtained, 16 were classified as affected for the purposes of linkage analysis."
Sixteen affected relatives were selected among 48 genotyped family members; this is the linkage ascertainment count, not the denominator for every clinical test.
High-Frequency Hearing Loss Progressing to All Frequencies Ear HP:0001757 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is High-frequency sensorineural hearing impairment progressing to all frequencies, annotated with High-frequency sensorineural hearing impairment (HP:0001757), qualified as laterality bilateral; course progressive. HP:0001757 is a phenotype from the Human Phenotype Ontology.
Laterality: BILATERAL Course: PROGRESSIVE
Show evidence (2 references)
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"DFNA53 is characterised by hearing loss affecting high frequencies that begins in the second decade of life and progresses to severe deafness involving all frequencies."
The frequency pattern that this phenotype records.
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"Affected individuals had sloping, flat, or residual audiograms (table 1)."
The audiogram configurations observed across the family.
🧬

Genetic Associations

1
DFNA53 locus at 14q11.2-q12 (Linkage analysis yielded a maximum two-point LOD score of 3.8 at theta = 0 for D14S608 and a maximum multipoint score of 5.4 at D14S1280. The causal gene and variant are unidentified.)
relationship_type: UNKNOWN variant_origin: GERMLINE
Affected regions (reference genome)
DFNA53 critical interval 14q11.2-q12
The recombinant-marker interval D14S581–D14S1021 spans 9.6 cM; the original mapping estimated a physical span of approximately 6.4 Mb. It overlaps the DFNA9 region. These are historical linkage and assembly measurements.
Show evidence (5 references)
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"positive LOD scores were obtained for the markers D14S1041, D14S1280, D14S615, and D14S608, with a maximum two point LOD score of 3.8 at θ = 0 for marker D14S608 (table 2) and a maximum multipoint LOD score of 5.4 at D14S1280"
The linkage evidence that defines the locus.
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"Screening of the COCH gene (DFNA9), BOCT, EFS, and HSPC156 within the DFNA53 interval did not identify the cause for deafness in this family."
No cause was found in the assayed coding regions and adjacent splice boundaries; this does not exclude every possible variant in these genes.
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"Identifying the DFNA53 locus is the first step in isolating the gene responsible for hearing loss in this large multigeneration Chinese family."
The authors' own statement that the gene had not been identified.
+ 2 more references
🗃️

External Assertions

1
MedGen concept for autosomal dominant nonsyndromic hearing loss 53
MedGen disease record MEDGEN:355336
MedGen identifies DFNA53 as the chromosome-region-defined concept corresponding to MONDO:0012380 and OMIM:609965. Its aggregated vestibular feature tag should be interpreted against the original report, which found normal caloric responses in six tested relatives.
Show evidence (1 reference)
url:https://www.ncbi.nlm.nih.gov/medgen/355336 SUPPORT Other
"An autosomal dominant nonsyndromic deafness that has material basis in variation in the chromosome region 14q11.2-q12."
The definition, which names a chromosome region and no gene.
💊

Medical Actions

5
Hearing Aids and Communication Support
Action: hearing aid fittingNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is hearing aid fitting, 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
Hearing aids can be tailored to hearing thresholds and communication goals. General genetic hearing-loss care also supports sign language or other communication methods according to individual and family preferences. The DFNA53 mapping report does not report rehabilitation outcomes.
Show evidence (2 references)
url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader SUPPORT REVIEW SYNTHESIS Human Clinical
"Habilitation for hearing loss includes improved access to sound through hearing aids or cochlear implants and, when desired, exposure to and teaching of American Sign Language."
The general habilitation options for genetic hearing loss, cited as class-level care.
url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader SUPPORT REVIEW SYNTHESIS Human Clinical
"Hearing aids (sound amplification), ... customized by an audiologist to the degree and frequency of hearing loss, can be used in individuals with mild-to-severe hearing loss."
General hearing-aid guidance; no DFNA53-specific response data are available in the mapping report.
Cochlear Implantation
Action: cochlear device implantationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is cochlear device 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
Cochlear implantation is a general rehabilitation option when the degree of hearing loss and individual audiologic assessment support candidacy. The mapping report does not describe implant outcomes, so benefit cannot be predicted specifically for DFNA53 from these sources.
Show evidence (1 reference)
url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader SUPPORT REVIEW SYNTHESIS Human Clinical
"Adults who communicate with spoken language most often seek to restore hearing using hearing aids, cochlear implants, gene therapy, or a combination of modalities."
Supports implantation as a general option for postlingual hearing loss in adults.
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. NCIT:C15240
Platform: Behavioral / lifestyle
Counselling should explain the dominant pedigree, the 50% allele-transmission probability under a heterozygous dominant model, variable expression and the unresolved causal gene. The 90% penetrance used for linkage is not an observed recurrence-risk estimate. Variant-specific predictive or reproductive testing requires identification of a causal variant.
Show evidence (2 references)
url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader SUPPORT REVIEW SYNTHESIS Human Clinical
"Individuals with autosomal dominant hearing loss have a 50% chance of transmitting the pathogenic variant to each child."
General autosomal dominant allele-transmission probability; this does not measure DFNA53 clinical penetrance.
url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader SUPPORT REVIEW SYNTHESIS Human Clinical
"Once the pathogenic variant(s) have been identified in the family, prenatal and preimplantation genetic testing for genetic hearing loss are possible."
General prerequisite for variant-specific reproductive testing; no causal DFNA53 variant is established.
Audiological Surveillance
Platform: Other
Serial audiologic assessment can document progression and guide hearing support. Relatives at increased familial risk should receive periodic testing even when the molecular cause remains unresolved; the interval is individualized rather than inferred from the age cutoff used in the original linkage model.
Show evidence (1 reference)
url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader SUPPORT REVIEW SYNTHESIS Human Clinical
"In the absence of a molecular diagnosis in the parent or sib with hearing loss, periodic audiologic testing should be performed for family members with an increased chance of hearing loss."
General follow-up guidance applicable to a family with unresolved inherited hearing loss.
Avoidance of Repeated Excessive Noise Exposure
Platform: Behavioral / lifestyle
Counsel about limiting repeated excessive noise exposure as part of general hearing conservation. No DFNA53-specific noise susceptibility or disease-modifying benefit has been established.
Show evidence (1 reference)
url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader SUPPORT REVIEW SYNTHESIS Human Clinical
"Since this risk can be minimized by avoidance, persons with documented hearing loss should be counseled appropriately and repeated overexposure to loud noises should be avoided."
General hearing-conservation advice, not evidence of a DFNA53-specific environmental mechanism.
🔬

Diagnosis

2
Audiometric and pedigree diagnosis
Clinical assessment in the original pedigree combined otoscopy, pure-tone air- and bone-conduction audiometry, oto-immittance, DPOAE and pedigree analysis. History and examination assessed acquired causes and syndromic features. DFNA53 attribution requires evidence connecting the family to the mapped locus; a similar audiogram or a negative gene panel alone does not establish this diagnosis.
Show evidence (2 references)
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"Otoscopic examination was done, and air conduction threshold measurements made at 250 Hz, 500 Hz, 1 kHz, 2 kHz, 4 kHz, 6 kHz, and 8 kHz."
The audiometric protocol used to classify affected status in the family.
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"The clinical history was taken and a physical examination carried out on the family members by one of the investigators, with special emphasis on identifying potential environmental causes of hearing loss such as infections, trauma, and exposure to ototoxic drugs including aminoglycoside and..."
History and examination screened for acquired causes and syndromic features; this is not proof that every possible alternative was excluded.
Genetic evaluation of an unresolved hearing-loss pedigree
General genetic hearing-loss evaluation can use a multigene panel and/or genomic testing to identify established causes with overlapping phenotypes. DFNA53 currently lacks an identified causal variant for a gene-specific diagnostic assay. A negative result leaves the etiology unresolved rather than proving DFNA53.
Show evidence (1 reference)
url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader SUPPORT REVIEW SYNTHESIS Human Clinical
"Recommended molecular genetic testing approaches ... include use of a ... multigene hearing loss panel ... and/or ... genomic testing"
General diagnostic approaches for genetic hearing loss; not a DFNA53-specific molecular test.
📈

Progression

2
Onset in the second decade
Most affected relatives reported onset in the second decade. Relatives younger than 15 without hearing loss were coded as phenotype-unknown for linkage, reflecting possible later onset. Postlingual onset does not establish normal thresholds throughout early childhood or an absolute lower age boundary.
Show evidence (1 reference)
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"At‐risk individuals without hearing loss who were under the age of 15 were considered to have an unknown phenotype with respect to the trait."
An age-dependent phenotype-coding choice in the linkage model, not a clinical surveillance schedule or proof that a normal childhood audiogram has no value.
Gradual progression to profound loss involving all frequencies
The report describes gradual progression and marked variation in expressivity. Its clinical table records individuals aged 14–67 with mild through profound loss, and sloping, flat or residual audiograms. The 2023 review summarizes progression to profound loss by the fourth or fifth decade, but this is not a precise prognosis for each family member.
Show evidence (2 references)
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"Hearing loss was variable, not only between generations but also within generations, demonstrating the substantial variation in phenotypic expressivity of DFNA53."
The variability that limits what can be said about an individual's course.
PMID:37371710 SUPPORT REVIEW SYNTHESIS Human Clinical
"HL is initially mild and limited to high frequencies but gradually involves all frequencies and progresses to a profound degree by the 4th/5th decade of life"
A 2023 review's summary of the DFNA53 time course, which puts a decade range on the endpoint that the primary report does not state.
📊

Prevalence

1
Reported northern Chinese family
Cases In Literature
The mapping report describes one six-generation family. It provides a literature case description, not a population prevalence estimate or a frequency band.
Show evidence (1 reference)
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"We investigated a six generation family from the northern part of China with autosomal dominant sensorineural hearing impairment."
Identifies the family studied; no population denominator was reported.
🔀

Differential Diagnoses

3

Conditions with similar clinical presentations that must be differentiated from Autosomal Dominant Nonsyndromic Hearing Loss 53:

Other autosomal dominant nonsyndromic hearing loss loci with the same audiometric pattern
Overlapping Features Several established autosomal dominant hearing-loss disorders share the progressive high-frequency pattern. A comprehensive hearing-loss panel or genomic analysis may identify an alternative cause. Negative testing does not establish linkage to DFNA53; evidence for the mapped interval must be evaluated separately.
Show evidence (1 reference)
PMID:15958501 SUPPORT PRIMARY RESULT Human Clinical
"This hearing phenotype is also observed in other previously identified ADNSSHL loci, including DFNA2, DFNA5, DFNA7, and DFNA9."
Names the loci sharing the audiometric pattern.
{ }

Source YAML

click to show 
name: Autosomal Dominant Nonsyndromic Hearing Loss 53
category: Mendelian
creation_date: '2026-09-26T00:00:00Z'
synonyms:
- DFNA53
- autosomal dominant deafness 53
- autosomal dominant nonsyndromic deafness 53
- autosomal dominant nonsyndromic deafness type 53
- deafness, autosomal dominant 53
- deafness, autosomal dominant nonsyndromic sensorineural 53
disease_term:
  preferred_term: autosomal dominant nonsyndromic hearing loss 53
  term:
    id: MONDO:0012380
    label: autosomal dominant nonsyndromic hearing loss 53
parents:
- Autosomal Dominant Nonsyndromic Hearing Loss
description: DFNA53 is a linkage-defined form of autosomal dominant nonsyndromic hearing loss mapped to 14q11.2-q12 in a six-generation family from northern China. Sixteen of 48 genotyped relatives were classified as affected. Hearing loss was bilateral, postlingual and progressive, usually beginning in the second decade, with substantial variability in severity and audiogram shape. Distortion product otoacoustic emissions demonstrated cochlear dysfunction, and caloric responses were normal in the six affected relatives tested. The causal gene and variant remain unidentified in the reviewed sources; the 2023 DFNA review lists both gene and protein function as unknown. Coding-region and splice-boundary screening of four candidate genes did not identify the cause.
references:
- reference: PMID:15958501
  title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
- reference: PMID:20301607
  title: Genetic Hearing Loss Overview.
  tags:
  - GeneReviews
- reference: PMID:37371710
  title: 'Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review.'
- reference: url:https://pmc.ncbi.nlm.nih.gov/articles/PMC2564639/table/tbl1/
  title: Table - PMC
inheritance:
- name: Autosomal dominant
  description: Hearing loss segregated as an autosomal dominant trait in three testable generations of a six-generation pedigree. The linkage analysis assumed 90% penetrance in heterozygotes; this was not a measured penetrance estimate. Under a heterozygous dominant model, each child has a 50% chance of inheriting the allele, which is distinct from the age-dependent chance of manifesting hearing loss. No causal variant has been established for variant-specific predictive testing.
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  evidence:
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The clinical history and audiological finding of the hearing loss in family members clearly revealed an autosomal dominant form of post‐lingual, bilateral sensorineural hearing loss.
    explanation: States the mode of inheritance and the character of the hearing loss in the only reported family.
    quote_role: PRIMARY_RESULT
  - &id001
    reference: url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader
    reference_title: Genetic Hearing Loss Overview - GeneReviews® - NCBI Bookshelf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Individuals with autosomal dominant hearing loss have a 50% chance of transmitting the pathogenic variant to each child.
    explanation: General autosomal dominant allele-transmission probability; this does not measure DFNA53 clinical penetrance.
    quote_role: REVIEW_SYNTHESIS
pathophysiology:
- name: Unidentified Dominant Allele in the 14q11.2-q12 Interval
  biological_scale: MOLECULAR
  mechanism_confidence: PROVISIONAL
  description: Linkage and recombinant haplotype analysis mapped DFNA53 between D14S581 and D14S1021, a 9.6 cM interval at 14q11.2-q12. The original assembly placed approximately 6.4 Mb and 60 known genes in this interval. A maximum multipoint LOD score of 5.4 supports linkage in the reported pedigree, but the causal gene, variant and molecular mechanism remain unresolved.
  notes: The original study sequenced coding regions and adjacent splice boundaries of COCH, SLC22A17 (BOCT), EFS and HSPC156 (STXBP6) without identifying a segregating cause. This screen did not comprehensively assess structural or noncoding variation; the authors explicitly noted unscreened COCH promoter and untranslated regions and the limitations for large deletions or duplications.
  downstream:
  - target: Cochlear Dysfunction
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Linkage to the interval and cochlear dysfunction were observed in the same family; the intervening molecular and cellular events are unknown.
    evidence:
    - reference: PMID:15958501
      reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Distortion product otoacoustic emission (DPOAE) testing in all the affected individuals, using the IL096 DP analyser (Otodynamics UK 1996), showed cochlear dysfunction.
      explanation: The cochlear localisation observed in the same affected individuals whose haplotypes define the locus.
      quote_role: PRIMARY_RESULT
  evidence:
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: This analysis placed the DFNA53 locus between the proximal marker D14S581 and the distal marker D14S1021, which defines a critical interval of 9.6 cM
    explanation: Defines the interval that this node names.
    quote_role: PRIMARY_RESULT
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: This interval spans a physical distance of about 6.4 Mb, and includes ∼60 known genes and a series of predicted or poorly characterised genes
    explanation: Historical physical span and gene count reported in the mapping study; not a current genome-assembly coordinate definition.
    quote_role: PRIMARY_RESULT
- name: Cochlear Dysfunction
  biological_scale: TISSUE
  description: Distortion product otoacoustic emission testing showed cochlear dysfunction in the affected relatives. Air- and bone-conduction audiometry and oto-immittance were used to assess the sensorineural character of the hearing loss. These findings support cochlear involvement but do not identify a particular cellular lesion or exclude all coexisting retrocochlear dysfunction.
  locations:
  - preferred_term: cochlea
    term:
      id: UBERON:0001844
      label: cochlea
  downstream:
  - target: Postlingual Progressive Sensorineural Hearing Loss
    description: The cochlear lesion is what the audiometric phenotype measures.
    evidence:
    - reference: PMID:15958501
      reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: The clinical history and audiological finding of the hearing loss in family members clearly revealed an autosomal dominant form of post‐lingual, bilateral sensorineural hearing loss.
      explanation: The sensorineural, postlingual character of the loss that the cochlear finding accounts for.
      quote_role: PRIMARY_RESULT
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: High-Frequency Hearing Loss Progressing to All Frequencies
    description: The frequency pattern of a progressive cochlear lesion, beginning at the high frequencies and extending downward.
    evidence:
    - reference: PMID:15958501
      reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: DFNA53 is characterised by hearing loss affecting high frequencies that begins in the second decade of life and progresses to severe deafness involving all frequencies.
      explanation: The frequency pattern and its progression, stated by the authors as the defining feature.
      quote_role: PRIMARY_RESULT
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  evidence:
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Distortion product otoacoustic emission (DPOAE) testing in all the affected individuals, using the IL096 DP analyser (Otodynamics UK 1996), showed cochlear dysfunction.
    explanation: The direct observation this node records.
    quote_role: PRIMARY_RESULT
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Bone conduction thresholds were determined to exclude a conductive component in patients with hearing loss.
    explanation: The study assessed bone-conduction thresholds to evaluate a possible conductive component; this is a diagnostic method, not direct molecular evidence.
    quote_role: PRIMARY_RESULT
phenotypes:
- name: Postlingual Progressive Sensorineural Hearing Loss
  category: Ear
  description: Postlingual bilateral sensorineural hearing loss was reported in the 16 affected relatives selected for linkage analysis. Most reported onset in the second decade; the earliest clinical evidence was at age 14 in two relatives. Severity ranged from mild to profound, with variable expressivity within and between generations. These selected affected cases do not estimate penetrance or population frequency.
  phenotype_term:
    preferred_term: Postlingual progressive sensorineural hearing impairment
    term:
      id: HP:0008596
      label: Postlingual sensorineural hearing impairment
    clinical_course: PROGRESSIVE
    laterality: BILATERAL
  evidence:
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The reported onset of hearing problems in most cases was in the second decade of life with subsequent gradual progression from mild to profound hearing loss involving the high frequencies in the majority of patients.
    explanation: Onset, severity range and progression in the only reported family.
    quote_role: PRIMARY_RESULT
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The earliest clinical evidence of hearing loss in the family was obtained from individuals V‐82 and V‐91 at the age of 14 years.
    explanation: The youngest documented age at onset, which is what a paediatric assessment turns on.
    quote_role: PRIMARY_RESULT
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Of the 48 individuals in whom DNA was obtained, 16 were classified as affected for the purposes of linkage analysis.
    explanation: Sixteen affected relatives were selected among 48 genotyped family members; this is the linkage ascertainment count, not the denominator for every clinical test.
    quote_role: PRIMARY_RESULT
- name: High-Frequency Hearing Loss Progressing to All Frequencies
  category: Ear
  description: The loss begins at the high frequencies and extends to involve all frequencies as it progresses. Audiogram configurations across the family were sloping, flat or residual. The authors note that this pattern is shared with several other ADNSHL loci and with presbycusis, which is part of why the entity is hard to recognise outside a large pedigree.
  phenotype_term:
    preferred_term: High-frequency sensorineural hearing impairment progressing to all frequencies
    term:
      id: HP:0001757
      label: High-frequency sensorineural hearing impairment
    clinical_course: PROGRESSIVE
    laterality: BILATERAL
  evidence:
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: DFNA53 is characterised by hearing loss affecting high frequencies that begins in the second decade of life and progresses to severe deafness involving all frequencies.
    explanation: The frequency pattern that this phenotype records.
    quote_role: PRIMARY_RESULT
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Affected individuals had sloping, flat, or residual audiograms (table 1).
    explanation: The audiogram configurations observed across the family.
    quote_role: PRIMARY_RESULT
prevalence:
- population: Reported northern Chinese family
  measure_type: CASES_IN_LITERATURE
  notes: The mapping report describes one six-generation family. It provides a literature case description, not a population prevalence estimate or a frequency band.
  evidence:
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: We investigated a six generation family from the northern part of China with autosomal dominant sensorineural hearing impairment.
    explanation: Identifies the family studied; no population denominator was reported.
    quote_role: PRIMARY_RESULT
progression:
- phase: Onset in the second decade
  notes: Most affected relatives reported onset in the second decade. Relatives younger than 15 without hearing loss were coded as phenotype-unknown for linkage, reflecting possible later onset. Postlingual onset does not establish normal thresholds throughout early childhood or an absolute lower age boundary.
  evidence:
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: At‐risk individuals without hearing loss who were under the age of 15 were considered to have an unknown phenotype with respect to the trait.
    explanation: An age-dependent phenotype-coding choice in the linkage model, not a clinical surveillance schedule or proof that a normal childhood audiogram has no value.
    quote_role: PRIMARY_RESULT
- phase: Gradual progression to profound loss involving all frequencies
  notes: The report describes gradual progression and marked variation in expressivity. Its clinical table records individuals aged 14–67 with mild through profound loss, and sloping, flat or residual audiograms. The 2023 review summarizes progression to profound loss by the fourth or fifth decade, but this is not a precise prognosis for each family member.
  evidence:
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Hearing loss was variable, not only between generations but also within generations, demonstrating the substantial variation in phenotypic expressivity of DFNA53.
    explanation: The variability that limits what can be said about an individual's course.
    quote_role: PRIMARY_RESULT
  - reference: PMID:37371710
    reference_title: 'Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: HL is initially mild and limited to high frequencies but gradually involves all frequencies and progresses to a profound degree by the 4th/5th decade of life
    explanation: A 2023 review's summary of the DFNA53 time course, which puts a decade range on the endpoint that the primary report does not state.
    quote_role: REVIEW_SYNTHESIS
genetic:
- name: DFNA53 locus at 14q11.2-q12
  relationship_type: UNKNOWN
  variant_origin: GERMLINE
  association: Linkage analysis yielded a maximum two-point LOD score of 3.8 at theta = 0 for D14S608 and a maximum multipoint score of 5.4 at D14S1280. The causal gene and variant are unidentified.
  affected_regions:
  - name: DFNA53 critical interval
    chromosomal_region: 14q11.2-q12
    description: The recombinant-marker interval D14S581–D14S1021 spans 9.6 cM; the original mapping estimated a physical span of approximately 6.4 Mb. It overlaps the DFNA9 region. These are historical linkage and assembly measurements.
  notes: The original study sequenced coding regions and adjacent splice boundaries of COCH, SLC22A17 (BOCT), EFS and HSPC156 (STXBP6) without identifying a segregating cause. This screen did not comprehensively assess structural or noncoding variation; the authors explicitly noted unscreened COCH promoter and untranslated regions and the limitations for large deletions or duplications.
  evidence:
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: positive LOD scores were obtained for the markers D14S1041, D14S1280, D14S615, and D14S608, with a maximum two point LOD score of 3.8 at θ = 0 for marker D14S608 (table 2) and a maximum multipoint LOD score of 5.4 at D14S1280
    explanation: The linkage evidence that defines the locus.
    quote_role: PRIMARY_RESULT
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Screening of the COCH gene (DFNA9), BOCT, EFS, and HSPC156 within the DFNA53 interval did not identify the cause for deafness in this family.
    explanation: No cause was found in the assayed coding regions and adjacent splice boundaries; this does not exclude every possible variant in these genes.
    quote_role: PRIMARY_RESULT
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Identifying the DFNA53 locus is the first step in isolating the gene responsible for hearing loss in this large multigeneration Chinese family.
    explanation: The authors' own statement that the gene had not been identified.
    quote_role: PRIMARY_RESULT
  - reference: PMID:37371710
    reference_title: 'Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: DFNA53 | 14q11.2–q12 | Unknown | Unknown. | Adolescence (2nd decade) | Sloping | Progressive
    explanation: A 2023 review tabulating every DFNA locus still lists the DFNA53 gene and its protein function as unknown, seventeen years after the mapping, which is the independent check on the primary report's own statement.
    quote_role: REVIEW_SYNTHESIS
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Two point linkage analysis was undertaken using the MLINK program from the LINKAGE package version 5.19 under an autosomal dominant mode of inheritance with 90% penetrance in the heterozygote, setting the disease allele frequency to 0.001 and considering the marker allele frequencies to be equal.
    explanation: The penetrance and allele frequency are analysis assumptions, not measured clinical or population estimates.
    quote_role: PRIMARY_RESULT
diagnosis:
- name: Audiometric and pedigree diagnosis
  description: Clinical assessment in the original pedigree combined otoscopy, pure-tone air- and bone-conduction audiometry, oto-immittance, DPOAE and pedigree analysis. History and examination assessed acquired causes and syndromic features. DFNA53 attribution requires evidence connecting the family to the mapped locus; a similar audiogram or a negative gene panel alone does not establish this diagnosis.
  evidence:
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Otoscopic examination was done, and air conduction threshold measurements made at 250 Hz, 500 Hz, 1 kHz, 2 kHz, 4 kHz, 6 kHz, and 8 kHz.
    explanation: The audiometric protocol used to classify affected status in the family.
    quote_role: PRIMARY_RESULT
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The clinical history was taken and a physical examination carried out on the family members by one of the investigators, with special emphasis on identifying potential environmental causes of hearing loss such as infections, trauma, and exposure to ototoxic drugs including aminoglycoside and noise, or for evidence of syndromic forms of deafness.
    explanation: History and examination screened for acquired causes and syndromic features; this is not proof that every possible alternative was excluded.
    quote_role: PRIMARY_RESULT
- name: Genetic evaluation of an unresolved hearing-loss pedigree
  description: General genetic hearing-loss evaluation can use a multigene panel and/or genomic testing to identify established causes with overlapping phenotypes. DFNA53 currently lacks an identified causal variant for a gene-specific diagnostic assay. A negative result leaves the etiology unresolved rather than proving DFNA53.
  evidence:
  - reference: url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader
    reference_title: Genetic Hearing Loss Overview - GeneReviews® - NCBI Bookshelf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Recommended molecular genetic testing approaches ... include use of a ... multigene hearing loss panel ... and/or ... genomic testing
    explanation: General diagnostic approaches for genetic hearing loss; not a DFNA53-specific molecular test.
    quote_role: REVIEW_SYNTHESIS
treatments:
- name: Hearing Aids and Communication Support
  therapeutic_modality: DEVICE
  description: Hearing aids can be tailored to hearing thresholds and communication goals. General genetic hearing-loss care also supports sign language or other communication methods according to individual and family preferences. The DFNA53 mapping report does not report rehabilitation outcomes.
  treatment_term:
    preferred_term: hearing aid fitting
    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: url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader
    reference_title: Genetic Hearing Loss Overview - GeneReviews® - NCBI Bookshelf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Habilitation for hearing loss includes improved access to sound through hearing aids or cochlear implants and, when desired, exposure to and teaching of American Sign Language.
    explanation: The general habilitation options for genetic hearing loss, cited as class-level care.
    quote_role: REVIEW_SYNTHESIS
  - reference: url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader
    reference_title: Genetic Hearing Loss Overview - GeneReviews® - NCBI Bookshelf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Hearing aids (sound amplification), ... customized by an audiologist to the degree and frequency of hearing loss, can be used in individuals with mild-to-severe hearing loss.
    explanation: General hearing-aid guidance; no DFNA53-specific response data are available in the mapping report.
    quote_role: REVIEW_SYNTHESIS
- name: Cochlear Implantation
  therapeutic_modality: SURGERY
  description: Cochlear implantation is a general rehabilitation option when the degree of hearing loss and individual audiologic assessment support candidacy. The mapping report does not describe implant outcomes, so benefit cannot be predicted specifically for DFNA53 from these sources.
  treatment_term:
    preferred_term: cochlear device 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: url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader
    reference_title: Genetic Hearing Loss Overview - GeneReviews® - NCBI Bookshelf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Adults who communicate with spoken language most often seek to restore hearing using hearing aids, cochlear implants, gene therapy, or a combination of modalities.
    explanation: Supports implantation as a general option for postlingual hearing loss in adults.
    quote_role: REVIEW_SYNTHESIS
- name: Genetic Counselling
  therapeutic_modality: BEHAVIORAL
  description: Counselling should explain the dominant pedigree, the 50% allele-transmission probability under a heterozygous dominant model, variable expression and the unresolved causal gene. The 90% penetrance used for linkage is not an observed recurrence-risk estimate. Variant-specific predictive or reproductive testing requires identification of a causal variant.
  treatment_term:
    preferred_term: Genetic Counseling
    term:
      id: NCIT:C15240
      label: Genetic Counseling
  evidence:
  - *id001
  - reference: url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader
    reference_title: Genetic Hearing Loss Overview - GeneReviews® - NCBI Bookshelf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Once the pathogenic variant(s) have been identified in the family, prenatal and preimplantation genetic testing for genetic hearing loss are possible.
    explanation: General prerequisite for variant-specific reproductive testing; no causal DFNA53 variant is established.
    quote_role: REVIEW_SYNTHESIS
- name: Audiological Surveillance
  description: Serial audiologic assessment can document progression and guide hearing support. Relatives at increased familial risk should receive periodic testing even when the molecular cause remains unresolved; the interval is individualized rather than inferred from the age cutoff used in the original linkage model.
  evidence:
  - reference: url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader
    reference_title: Genetic Hearing Loss Overview - GeneReviews® - NCBI Bookshelf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: In the absence of a molecular diagnosis in the parent or sib with hearing loss, periodic audiologic testing should be performed for family members with an increased chance of hearing loss.
    explanation: General follow-up guidance applicable to a family with unresolved inherited hearing loss.
    quote_role: REVIEW_SYNTHESIS
  therapeutic_modality: OTHER
- name: Avoidance of Repeated Excessive Noise Exposure
  description: Counsel about limiting repeated excessive noise exposure as part of general hearing conservation. No DFNA53-specific noise susceptibility or disease-modifying benefit has been established.
  evidence:
  - reference: url:https://www.ncbi.nlm.nih.gov/sites/books/NBK1434/?report=reader
    reference_title: Genetic Hearing Loss Overview - GeneReviews® - NCBI Bookshelf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Since this risk can be minimized by avoidance, persons with documented hearing loss should be counseled appropriately and repeated overexposure to loud noises should be avoided.
    explanation: General hearing-conservation advice, not evidence of a DFNA53-specific environmental mechanism.
    quote_role: REVIEW_SYNTHESIS
  therapeutic_modality: BEHAVIORAL
differential_diagnoses:
- name: DFNA9, COCH-related hearing loss
  description: DFNA9 overlaps the mapped interval and can produce a similar progressive audiogram. The original DFNA53 family had no reported vestibular dysfunction and normal caloric responses in six tested relatives. However, vestibular involvement in DFNA9 is variable, so its absence alone is not a definitive exclusion. The original COCH screen assessed coding regions and splice boundaries, not all structural or regulatory variants.
  evidence:
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Although, there is some similarity in the audiograms of DFNA53 patients in comparison with those of patients with DFNA9, none of the affected members (14 to 67 years of age) in the DFNA53 family showed vestibular dysfunction.
    explanation: The clinical feature that separates the two, across the full age range of the family.
    quote_role: PRIMARY_RESULT
  - reference: PMID:37371710
    reference_title: 'Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: HL is associated with variable vestibular dysfunction and tends to progress to anacusis by the 5th decade of life
    explanation: The DFNA9 table row describes variable vestibular involvement; a normal vestibular examination alone does not rule out COCH-related disease.
    quote_role: REVIEW_SYNTHESIS
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: There was no evidence for an effect of sex on progression, and six affected subjects of the family underwent caloric testing with normal results (table 1).
    explanation: The normal caloric finding applies to six tested affected relatives.
    quote_role: PRIMARY_RESULT
- name: Age-related hearing loss (presbycusis)
  description: Progressive high-frequency loss extending to all frequencies is also the pattern of presbycusis, which is common enough that a dominant pedigree can be mistaken for coincidental aggregation in an older family. The distinguishing features are the age at onset - second decade rather than later adult life - and the clear vertical transmission through several generations.
  evidence:
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: High frequency hearing loss that progresses to involve all frequencies is characteristic of age related hearing loss, also known as presbycusis.
    explanation: The overlap the authors themselves name.
    quote_role: PRIMARY_RESULT
- name: Other autosomal dominant nonsyndromic hearing loss loci with the same audiometric pattern
  description: Several established autosomal dominant hearing-loss disorders share the progressive high-frequency pattern. A comprehensive hearing-loss panel or genomic analysis may identify an alternative cause. Negative testing does not establish linkage to DFNA53; evidence for the mapped interval must be evaluated separately.
  evidence:
  - reference: PMID:15958501
    reference_title: A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: This hearing phenotype is also observed in other previously identified ADNSSHL loci, including DFNA2, DFNA5, DFNA7, and DFNA9.
    explanation: Names the loci sharing the audiometric pattern.
    quote_role: PRIMARY_RESULT
discussions:
- discussion_id: dfna53_causal_gene_unidentified
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#Unidentified Dominant Allele in the 14q11.2-q12 Interval
  - genetic#DFNA53 locus at 14q11.2-q12
  prompt: Which causal variant and gene account for the hearing-loss linkage at 14q11.2-q12, and can independent families replicate the association?
  rationale: The mapping study provides strong linkage evidence within one pedigree but does not resolve a gene or molecular mechanism. Its coding-region candidate screen left structural and regulatory variation incompletely assessed. Genome analysis could revisit these possibilities if appropriate samples are available, but sample availability is not established by the historical report.
  proposed_experiments:
  - experiment_id: dfna53_genome_sequencing_of_the_original_pedigree
    name: Genome sequencing of the original DFNA53 pedigree
    description: If samples and consent are available, sequence affected and informative unaffected relatives using genome methods that assess sequence and structural variation, then evaluate candidates within a remapped D14S581–D14S1021 interval. Account for age-dependent phenotype classification and assay coverage, and seek independent genetic and functional evidence.
    would_support:
    - pathophysiology#Unidentified Dominant Allele in the 14q11.2-q12 Interval
    supporting_outcome:
    - A rare segregating variant would nominate a candidate; replication and functional evidence consistent with the clinical phenotype would strengthen causal attribution.
    refuting_outcome:
    - Reliable segregation incompatible with the interval or stronger evidence for a different cause would weaken the original locus assignment. Failure to detect a variant alone would remain inconclusive because of assay and interpretation limits.
external_assertions:
- name: MedGen concept for autosomal dominant nonsyndromic hearing loss 53
  source: MedGen
  assertion_type: disease_record
  external_id: MEDGEN:355336
  url: https://www.ncbi.nlm.nih.gov/medgen/355336
  description: MedGen identifies DFNA53 as the chromosome-region-defined concept corresponding to MONDO:0012380 and OMIM:609965. Its aggregated vestibular feature tag should be interpreted against the original report, which found normal caloric responses in six tested relatives.
  evidence:
  - reference: url:https://www.ncbi.nlm.nih.gov/medgen/355336
    reference_title: 'Autosomal dominant nonsyndromic hearing loss 53 (Concept Id: C1864957) - MedGen - NCBI'
    supports: SUPPORT
    evidence_source: OTHER
    snippet: An autosomal dominant nonsyndromic deafness that has material basis in variation in the chromosome region 14q11.2-q12.
    explanation: The definition, which names a chromosome region and no gene.
notes: Disease-specific clinical and linkage evidence comes from the original family report; the 2023 review supplies secondary context and GeneReviews supplies general care. No causal gene, validated variant-specific model or disease-specific treatment is established by these sources. Candidate-screening negatives are limited to the regions and methods tested. Normal caloric responses in six relatives should not be converted into a positive vestibular phenotype from an aggregated database tag.
📚

References & Deep Research

References

4
PMID:15958501
A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to chromosome 14q11.2-q12.
No top-level findings curated for this source.
PMID:20301607
Genetic Hearing Loss Overview.
No top-level findings curated for this source.
PMID:37371710
Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review.
No top-level findings curated for this source.
No top-level findings curated for this source.

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)

Review DFNA53 linkage, phenotype scope and general hearing-loss care · 2026-09-27T22:56:07Z · View source

Reviewed the existing entry and CREATE history, the scientific deep-research narrative and citation leads, PMID:15958501 full text and its recovered clinical Table 1, the complete PMID:37371710 review and table, and the GeneReviews overview clinical, genetic and management narrative and tables. The primary table describes 16 affected relatives aged 14–67; six had normal caloric tests. Recovered the table with just fetch-reference. Manual identity checks confirm MONDO:0012380 / OMIM:609965 and an unresolved causal gene. Automated preflight returned SKIP because MONDO has no causal-gene relation. Corrected overstated candidate-gene exclusion, DPOAE localization, childhood hearing, phenotype-frequency and prevalence bands, diagnosis by exclusion, and proposed genome-study proof. Preserved historical linkage statistics while separating assumed 90% penetrance and allele frequency 0.001 from measured observations. Added general genetic-testing guidance, hearing-aid evidence, periodic familial audiology and noise conservation from GeneReviews. The 50% figure describes allele transmission rather than measured clinical penetrance. DFNA9 vestibular involvement is variable. The research report incorrectly described vestibular function as untested, missed the DPOAE result, and suggested unsupported hair-cell mechanisms and an incorrect cochlea term; these claims were not adopted. Completeness assessment: phenotype coverage is adequate for the source (two audiometric manifestations and explicit normal caloric findings); established subtypes are not reported. Mechanisms remain limited to a provisional unidentified allele and observed cochlear dysfunction. Care was expanded without inventing DFNA53 treatment responses. Genetics now states method limits and model assumptions; diagnostics distinguishes genetic evaluation from establishing this locus. All relevant available cached scientific content was consumed. The reviewed sources establish no causal variant, experimental disease model, disease-specific trial or targeted therapy. General GeneReviews care is distinguished from disease-specific evidence; the tagged overview informed clinical interpretation, diagnosis, management, counseling and noise avoidance. Removed curation-process narrative from disease-facing notes; the historical CREATE scope decision remains available. Rebased onto main 99f8d60b5e5 before editing. Validation: schema, terms and references passed with 39 verified snippets and 43 titles; strict cached quotation checks, causal targets, entity references, coarse phenotypes, qualifiers and source-defect checks passed.

Create: Autosomal_Dominant_Nonsyndromic_Hearing_Loss_53 · 2026-09-26T23:49:01Z · View source

Curated DFNA53 as a deliberately thin Disease entry after establishing that it is a mapped linkage locus with no identified gene. Evidence base: PMID:15958501 (the single published report; PubMed returns exactly one record for DFNA53), PMID:37371710 (2023 DFNA narrative review, whose locus table still lists the gene as unknown), and the GeneReviews Genetic Hearing Loss Overview for class-level care. No ClinGen gene-disease validity assertion exists against MONDO:0012380; HPO and MedGen record no associated gene; MONDO's term is live and defines the entity by chromosome region. Four candidate genes (COCH, SLC22A17, EFS, HSPC156) were sequenced and excluded by the mapping study and none was adopted here. The pathograph runs from an explicitly unidentified 14q11.2-q12 allele (mechanism_confidence PROVISIONAL) through a cochlear-dysfunction node evidenced by DPOAE to the two audiometric phenotypes; no molecular mechanism is asserted. An OUT_OF_SCOPE ruling was considered and rejected; the reasoning against it, and the DFNB46 and DFNA47 precedents, are recorded in the entry notes. Deep research: falcon returned HTTP 402 (out of credits) and the claude_code fallback produced the report; preflight-dr returned SKIP (MONDO records no causal gene, so the gene-identity check cannot discriminate) with OMIM 609965 matching on both sides.

Claude Code ▸
1. Disease Information
claude-haiku-4-5-20251001, claude-sonnet-5 8 citations 2026-09-26T23:37:20.241392

1. Disease Information

Overview. DFNA53 designates an autosomal dominant, nonsyndromic (isolated) sensorineural hearing loss locus mapped to human chromosome 14q11.2–q12 in a single large, multigenerational Chinese family. The phenotype is postlingual (onset in adolescence/the second decade of life), begins as high-frequency hearing loss, and progresses to involve all frequencies, reaching a profound degree by the fourth–fifth decade of life (Yan et al., 2006, PMID:15958501; Aldè et al. 2023, PMC:PMC10296186).

"post-lingual, high frequency hearing loss that progresses to involve all frequencies" — Yan D et al., J Med Genet 2006;43(2):170-174.

"HL is initially mild and limited to high frequencies but gradually involves all frequencies and progresses to a profound degree by the 4th/5th decade of life." — Aldè et al., Audiology Research 2023 (DFNA locus table entry for DFNA53).

Key identifiers: | Resource | Identifier | |---|---| | OMIM | #609965 — DEAFNESS, AUTOSOMAL DOMINANT 53; DFNA53 | | MONDO | MONDO:0012380 | | MedGen | C1864957 (NCBI GTR: C1864957) | | GARD (NIH rare disease) | GARD ID 9934 | | Locus | 14q11.2–q12 | | Gene | Not identified |

Synonyms: Deafness, autosomal dominant 53; autosomal dominant nonsyndromic deafness 53; autosomal dominant nonsyndromic hearing loss 53.

Data provenance. All disease-level information available for DFNA53 derives from a single aggregated genetic-mapping study of one family (a case series/pedigree study), not from EHR-derived or population-registry data. There is no disease registry, no epidemiologic surveillance record, and no subsequent replication cohort.

2. Etiology

  • Disease causal factor: Presumed to be a single dominant (heterozygous) germline variant in an as-yet-unidentified gene within the 14q11.2–q12 interval, based on autosomal dominant segregation with a maximum multipoint LOD score of 5.4 at marker D14S1280 (PMID:15958501).
  • Genetic risk factors: Inheriting the disease haplotype from an affected parent; no specific variant, susceptibility locus, or modifier gene has been reported.
  • Environmental risk factors: None reported or investigated for this locus; no environmental co-factor has been described in the single published family.
  • Protective factors: Not studied.
  • Gene–environment interaction: Not studied. No data exist to assess this axis for DFNA53 specifically.

Candidate genes within the mapped interval that were explicitly excluded by direct screening in the original family are: - COCH (the DFNA9 gene, HGNC:2180) — the DFNA53 critical region contains the COCH locus, but sequencing did not identify a causative variant. - BOCT / SLC22A17 - EFS - HSPC156 / STXBP6

"the critical region for DFNA53 contains the gene for DFNA9 [COCH] but does not overlap with the regions for DFNB5, DFNA23, or DFNB35... screening of the COCH gene, BOCT (SLC22A17), EFS, and HSPC156 (STXBP6) within the DFNA53 interval did not identify the cause for deafness in this family" (Yan et al. 2006, PMID:15958501).

3. Phenotypes

Because only one family has been reported, phenotype "frequency" data (e.g., % of patients with a feature) does not exist in the population-genetics sense — the figures below describe the single pedigree's clinical course as reported.

Phenotype HPO suggestion Onset Course Notes
Postlingual sensorineural hearing loss HP:0008619 (Bilateral sensorineural hearing impairment) / HP:0000407 (Sensorineural hearing impairment) Adolescence, second decade of life Progressive Initial presentation
High-frequency-predominant hearing loss HP:0000407 combined with a sloping-configuration descriptor; no dedicated HPO term for "sloping audiogram" beyond general SNHL terms Onset Evolves Sloping audiometric configuration at onset
Progression to all-frequency, profound deafness HP:0008625 (Bilateral profound sensorineural hearing impairment) 4th–5th decade End-stage Progresses from high-frequency to pantonal loss
  • Phenotype type: Sensorineural hearing impairment (a clinical sign/laboratory-audiometric abnormality), not a syndromic constellation — the entry is explicitly "nonsyndromic," meaning no other organ system involvement was reported in the affected family.
  • Severity/progression: Progressive, sloping-to-flat/profound audiometric configuration, consistent with many other DFNA loci (Aldè et al. 2023, PMC10296186).
  • Vestibular function: The original 2006 report does not describe vestibular testing or vestibular symptoms. A downstream NCBI GTR/MedGen record lists "abnormal vestibular function" as an associated clinical feature for this condition, but this could not be traced to a specific statement in the primary Yan et al. paper during this search — flag this as an unverified, database-level tag rather than a confirmed primary-literature finding, and it should not be curated as evidence without independent confirmation.
  • Quality of life impact: Not studied for this specific family; no disease-specific QOL instrument data exist.

4. Genetic/Molecular Information

  • Causal gene: Unknown. No gene has been identified for DFNA53 in the ~20 years since the locus was mapped (confirmed by the current hereditaryhearingloss.org DFNA locus table, which lists DFNA53 as "gene unknown," and by the absence of any subsequent primary literature identifying a causal gene).
  • Locus: 14q11.2–q12, a 9.6 cM interval bounded by microsatellite markers D14S581 and D14S1021, with peak linkage (multipoint LOD 5.4) at D14S1280 (PMID:15958501).
  • Variant classification/type/allele frequency/somatic-vs-germline/functional consequence: Not applicable — no variant has been reported.
  • Modifier genes, epigenetic information, chromosomal abnormalities: None reported.
  • Relationship to other loci on 14q: Four other deafness loci map to the long arm of chromosome 14 — DFNA9 (COCH, sits inside the DFNA53 critical region but was excluded as causal), DFNA23, DFNB5, and DFNB35 — but the DFNA53 interval does not overlap the latter three (PMID:15958501). This makes DFNA53 genetically and physically distinct from its chromosome-14 neighbors even though it spatially contains the COCH gene.

5. Environmental Information

No environmental factors, lifestyle factors, or infectious agents have been reported or investigated in connection with DFNA53. As a monogenic, single-family, autosomal dominant mapping result, there is no literature addressing gene–environment modulation of this specific locus.

6. Mechanism / Pathophysiology

No mechanism can be constructed for DFNA53 with any specificity, because the causal gene is unknown. A causal chain cannot be drawn beyond the top-level genetic statement, and any lower step would be an inference from the general biology of nonsyndromic hearing loss rather than a demonstrated fact about this locus. Presenting a plausible-looking pathway here would misrepresent the state of evidence, so only the following is offered:

  1. A dominant germline variant at an unidentified gene in 14q11.2–q12 is inferred to disrupt inner-ear (most likely cochlear) structure or function — inferred, not demonstrated, from the clinical phenotype (progressive high-frequency-onset SNHL) by analogy to other DFNA loci with a similar audiometric trajectory.
  2. This putative dysfunction is inferred to initially and preferentially affect basal-turn (high-frequency-coding) cochlear hair cells or their supporting structures, given the high-frequency-first audiometric pattern — again inferred by analogy, not shown directly for this locus.
  3. Progression to pantonal, profound loss by the 4th–5th decade suggests a slowly progressive degenerative process rather than a static congenital lesion — inferred from the clinical course alone.

No molecular pathway, cellular process, protein dysfunction, metabolic change, immune involvement, tissue-damage mechanism, biochemical abnormality, epigenetic change, or any -omics profiling (transcriptomic, proteomic, metabolomic, lipidomic, single-cell, spatial) has been reported for DFNA53, because the causal gene — and therefore any tissue or cellular substrate to study — has never been identified. No GO or CL term can be responsibly assigned to a specific mechanistic step for this entry without fabricating specificity the source does not support.

7. Anatomical Structures Affected

  • Organ level: Inner ear (cochlea) — the only organ system reported as affected, consistent with the "nonsyndromic" designation (no other organ involvement reported). Body system: auditory/sensory (and, per the caveated GTR vestibular tag in §3, possibly vestibular — unconfirmed).
  • Anatomical term (UBERON): UBERON:0001846 (cochlea) is the most specific defensible anatomical anchor, since no cell-type-specific or subcellular-level finding has been reported.
  • Tissue/cell/subcellular level: No specific cell population (e.g., outer vs. inner hair cells, stria vascularis, spiral ganglion) or organelle has been implicated by any study — this would need to be inferred from a mechanism that does not yet exist for this locus (see §6).
  • Laterality: Bilateral, based on standard DFNA convention and the "sensorineural hearing impairment" HPO/GTR coding (bilateral is the default assumption for nonsyndromic genetic SNHL loci; not separately confirmed as bilateral vs. asymmetric in the primary paper's abstract).

8. Temporal Development

  • Onset: Postlingual, adolescence/second decade of life (PMID:15958501; Aldè et al. 2023).
  • Onset pattern: Insidious, not acute.
  • Progression: Progressive — initially mild, limited to high frequencies; gradually involves all frequencies; reaches profound severity by the 4th–5th decade of life (Aldè et al. 2023, PMC10296186).
  • Disease course pattern: Progressive, not episodic or relapsing-remitting; no data on plateaus or stable phases.
  • Remission: None reported (progressive sensorineural hearing loss of this type is not expected to remit).
  • Critical periods: Not established — no data on a window during which intervention alters outcome, though for any progressive postlingual SNHL, earlier identification of decline would generally be presumed clinically useful (a general inference, not DFNA53-specific evidence).

9. Inheritance and Population

  • Epidemiology: No prevalence or incidence estimate exists for DFNA53 specifically. It has been reported in exactly one family; DFNA loci collectively account for only a minority (roughly 20%) of hereditary nonsyndromic hearing loss, but no locus-specific frequency figure is available for DFNA53 (general DFNA-class context from Aldè et al. 2023, not DFNA53-specific).
  • Inheritance pattern: Autosomal dominant, based on classic segregation of the phenotype with the 14q11.2-q12 haplotype across multiple generations, with a maximum multipoint LOD score of 5.4 (PMID:15958501).
  • Penetrance: Not explicitly quantified in the abstract; the family structure implies high (if not complete) penetrance sufficient to generate a LOD score of 5.4, but no numeric penetrance estimate has been published.
  • Expressivity, anticipation, germline mosaicism, founder effects, consanguinity, carrier frequency: None reported/applicable — these require either multiple pedigrees or population data, neither of which exists for this single-family locus.
  • Population demographics: The single reported family is Chinese (Han Chinese, presumptively, based on recruitment context, though ethnicity beyond "Chinese family" is not further specified in the abstract). No other population, geographic distribution, sex ratio, or age-distribution data exist.

10. Diagnostics

No DFNA53-specific diagnostic test, biomarker, imaging finding, or histopathology has been described (there is no known gene to target with a single-gene or panel-based clinical test). General, non-locus-specific guidance applicable to any postlingual progressive autosomal dominant SNHL family would include:

  • Audiometry: Pure-tone audiometry to document the sloping-to-flat/pantonal progressive configuration — the primary phenotyping tool used in the original family study.
  • Genetic testing (general, not DFNA53-specific): Because no causal gene is known, a clinical multi-gene hereditary hearing loss panel or exome/genome sequencing would not currently include a targeted DFNA53 assay; family-specific linkage analysis (as performed in the original 2006 study, using markers such as D14S581, D14S1280, D14S1021) would be the only way to test for co-segregation with this specific chromosomal region in a new large family, but this is a research approach, not a clinical diagnostic offering.
  • Differential diagnosis: Other chromosome 14 DFNA loci in the region (DFNA9/COCH) should be excluded by direct gene sequencing before considering a novel-locus mapping study, exactly as was done in the original report.
  • Screening: No population or newborn screening applies to this ultra-rare, single-family locus.

11. Outcome/Prognosis

  • Survival/mortality: Not applicable — nonsyndromic hearing loss does not affect survival; no mortality data exist or would be expected.
  • Morbidity/function: Progressive profound sensorineural hearing loss by the 4th–5th decade would be expected to significantly affect communication function and quality of life, by general analogy to other progressive DFNA phenotypes, but no disease-specific functional-outcome or QOL data have been published for DFNA53.
  • Complications: None reported beyond the hearing loss itself (nonsyndromic — no other organ complications documented).
  • Prognostic factors/biomarkers: None established.

12. Treatment

No DFNA53-specific treatment or gene-targeted therapy exists (there is no identified gene to target). Management would follow the standard, non-locus-specific approach to progressive sensorineural hearing loss:

  • Amplification: Hearing aids as high-frequency loss becomes functionally significant — NCIT term candidate: NCIT:C-hearing aid device concept would be bound as a device, not a TreatmentTerm action, per standard NCIT device-vs-action handling (analogous devices are typically bound via the clinical-action + qualifiers pattern, e.g., "hearing aid fitting" bound to a general audiologic-rehabilitation action term with the device carried as a qualifier).
  • Cochlear implantation: Would be the standard intervention once loss progresses to a profound, aid-non-responsive level, following the general clinical pathway used for other progressive genetic SNHL loci — NCIT:C15329 (Surgical Procedure) is the appropriate clinical-action anchor for the implantation itself, per standard dismech convention for device-based interventions.
  • Audiologic rehabilitation/speech-language therapy: Standard supportive care for progressive hearing loss — NCIT:C15302 (Physical Therapy)/NCIT:C159273 (Speech Language Therapy) analogs, as used generically across other DFNA entries.
  • Genetic counseling: NCIT:C15240 (Genetic Counseling), given the confirmed autosomal dominant inheritance and 50% offspring recurrence risk (GARD summary).
  • Gene therapy, RNA-based therapy, targeted/precision therapy: Not applicable — no target gene exists to develop a molecular therapeutic against.
  • Clinical trials: No DFNA53-specific trial was found on ClinicalTrials.gov in this search.

All of the above is general standard-of-care inference for progressive nonsyndromic SNHL, not evidence specific to DFNA53, and should be labeled as such in any curation use.

13. Prevention

No DFNA53-specific primary, secondary, or tertiary prevention strategy exists. Standard genetic-counseling-based family planning guidance (informing at-risk relatives of the 50% autosomal dominant recurrence risk) is the only prevention-adjacent measure supported by the available literature (GARD summary page).

14. Other Species / Natural Disease

Not applicable/not available. Because the causal gene is unknown, no ortholog, veterinary correlate, or naturally occurring animal disease can be identified or excluded for DFNA53.

15. Model Organisms

None exist. With no causal gene identified, there is no mouse, zebrafish, or other genetic model of DFNA53, no knockout/knock-in resource, and no functional-genomics screen targeting this locus. This is a direct consequence of the locus never having been resolved to a gene, not a gap in searching.

Curation Guidance / Caveats for KB Use

  1. This is a locus-only OMIM entry with no gene. Any dismech genetic: block should record the 14q11.2–q12 locus context in notes, but should not invent a gene_term binding — there is none to bind.
  2. Single-family evidence. Every clinical/phenotypic claim above traces to one 2006 paper describing one pedigree. Treat prevalence, penetrance, and phenotype-frequency claims accordingly — there is no population-level denominator.
  3. The "abnormal vestibular function" GTR/MedGen tag is flagged, not confirmed. Do not cite it as primary-literature evidence without independently verifying it against the full OMIM clinical synopsis or original paper (this search could not access the full OMIM clinical synopsis due to a site-side block).
  4. No mechanism section should be written with GO/CL specificity for this entry beyond the caveated inferences in §6 — doing so would fabricate a mechanistic claim the source literature does not support.
  5. Per dismech's evidence policy, only PMID:15958501 (and the general-DFNA-context review PMC10296186, cited separately and clearly as general context) should be used as sources; no other primary literature on DFNA53 was found to exist as of this search (September 2026).

Sources

Reference Validation

Checked with linkml-reference-validator 0.3.0rc3.

Outcome Count
References checked 3
Resolved 3
Unresolved (possible confabulation) 0
Unverifiable 0
Quoted claims checked 1
Quoted claims found in source 0
Quoted claims not found in source 1
References weighed for topical relevance 3
On topic 3
Off topic 0

Quotes not found in the cited source

Searched the abstract, any retrieved full text, and the title. A quote drawn from a part of the paper that was not retrieved will appear here too, so check before treating one as invented:

  • PMID:15958501: "the critical region for DFNA53 contains the gene for DFNA9 [COCH] but does not overlap with the regions for DFNB5, DFNA23, or DFNB35... screening of the COCH gene, BOCT (SLC22A17), EFS, and HSPC156 (STXBP6) within the DFNA53 interval did not identify the cause for deafness in this family"
  • closest text in source: "The critical region for DFNA53 contains the gene for DFNA9 but does not overlap with the regions for DFNB5, DFNA23, or DFNB35"

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 10
Resolved 9
Unresolved (possible confabulation) 0
Obsolete 0
Unverifiable 1
Terms whose name was checked 7
Terms named correctly 4
Terms named as a different term 2
Terms whose name is worth a second look 1

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:0012380 (4 mentions) - the report calls it "MONDO", "OLS"; MONDO calls it autosomal dominant nonsyndromic hearing loss 53
  • UBERON:0001846 (1 mention) - the report calls it "cochlea"; UBERON calls it internal ear

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

  • HP:0008625 (1 mention) - the report calls it "Bilateral profound sensorineural hearing impairment"; HP calls it Severe sensorineural hearing impairment

Terms named inconsistently

The report gives these identifiers more than one name of its own:

  • MONDO:0012380 - called "MONDO", "OLS"