Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

• Disease Name: Autosomal Recessive Nonsyndromic Hearing Loss 79 (DFNB79, TPRN-related)
• MONDO ID: (if available)
• Category: Mendelian

Research Objectives

Please provide a comprehensive research report on Autosomal Recessive Nonsyndromic Hearing Loss 79 (DFNB79, TPRN-related) covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

• What is the disease? Provide a concise overview.
• What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
• What are the common synonyms and alternative names?
• Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

• Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
• Risk Factors:

  Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

• Genetic risk factors (causal variants, susceptibility loci, modifier genes)
• Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
• Protective Factors:

  Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

• Genetic protective factors (protective variants, modifier alleles)
• Environmental protective factors (diet, lifestyle, exposures that reduce risk)
• Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

  Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

• Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

  Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

• Pathogenic Variants:
• Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
• Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
• Variant type/class (missense, frameshift, nonsense, splice-site, structural)
• Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
• Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
• Functional consequences (loss of function, gain of function, dominant negative)
• Modifier Genes: Genes that modify disease severity or expression
• Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

  Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

• Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

  Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

• Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

  Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

• Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

  Search first: CDC databases, WHO, PubMed, NHANES

• Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

  Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

Present this section as an ordered causal chain first, then the detail below. Open with a numbered sequence of mechanistic steps running from the initiating lesion (mutation, exposure, infection) to the clinical manifestation, one step per line, each naming what it causes next. State the causal verb explicitly ("leads to", "results in") and say where a step is inferred rather than demonstrated. Where the mechanism branches, show the branch. The categories below are a checklist of what to cover within those steps, not the organizing structure — a step may draw on several of them, and a category may contribute to several steps.

• Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

  Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

• Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

  Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

• Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

  Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

• Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

  Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

• Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

  Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

• Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

  Search first: PubMed, Gene Ontology, Reactome

• Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

  Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

• Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

  Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

• Molecular Profiling (if available):
• Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
• Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
• Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
• Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
• Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
• Advanced Technologies (if applicable):
• Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
• Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
• Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
• Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

• Organ Level:
• Primary organs directly affected
• Secondary organ involvement (complications, secondary effects)
• Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

  Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

• Tissue and Cell Level:
• Specific tissue types affected (epithelial, connective, muscle, nervous)
• Specific cell populations targeted (with Cell Ontology terms)

  Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

• Subcellular Level:
• Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

  Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

• Localization:
• Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
• Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

• Onset:
• Typical age of onset (congenital, pediatric, adult, geriatric)
• Onset pattern (acute, subacute, chronic, insidious)

  Search first: OMIM, Orphanet, HPO, PubMed

• Progression:
• Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
• Progression rate (rapid, slow, variable)
• Disease course pattern (episodic, relapsing-remitting, progressive, stable)
• Disease duration (self-limited, chronic lifelong)

  Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

• Patterns:
• Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
• Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

• Epidemiology:
• Prevalence (cases per 100,000 at given time)
• Incidence (new cases per 100,000 per year)

  Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

• For Genetic Etiology:
• Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
• Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
• Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
• Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
• Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
• Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
• Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
• Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
• Population Demographics:
• Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
• Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
• Geographic distribution of specific variants
• Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
• Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

• Clinical Tests:
• Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
• Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
• Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
• Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
• Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
• Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
• Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
• Genetic Testing:

  Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

• Overview of recommended genetic testing approach
• Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
• Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
• Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
• Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
• Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
• Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
• FISH > Search first: ClinVar, cytogenetics databases, PubMed
• Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
• Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
• Omics-Based Diagnostics (if applicable):
• RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
• Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
• Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
• Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
• Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
• Clinical Criteria:
• Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
• Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
• Screening:
• Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

• Survival and Mortality:
• Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
• Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
• Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
• Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
• Morbidity and Function:
• Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
• Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
• Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
• Disease Course:
• Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
• Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
• Prediction:
• Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
• Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

• Pharmacotherapy:
• Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
• Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
• Advanced Therapeutics:
• Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
• Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
• RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
• Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
• Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
• Surgical and Interventional:
• Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
• Supportive and Rehabilitative:
• Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
• Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
• Experimental:
• Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
• Treatment Outcomes:
• Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
• Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
• Treatment Strategy:
• Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
• Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
• Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest NCIT (NCI Thesaurus) clinical-intervention terms where applicable.

13. Prevention

• Prevention Levels:
• Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
• Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
• Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
• Immunization: Vaccine strategies (if applicable)

  Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

• Screening and Early Detection:
• Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
• Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
• Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
• Behavioral Interventions: Lifestyle modifications to reduce risk

  Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

• Counseling: Genetic counseling (risk assessment, family planning guidance)

  Search first: NSGC resources, ACMG guidelines, GeneReviews

• Public Health:
• Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
• Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
• Prophylaxis: Preventive medications or procedures

  Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

• Taxonomy: Species affected (with NCBI Taxon identifiers)

  Search first: NCBI Taxonomy

• Breed: Specific breeds affected (with VBO identifiers if applicable)

  Search first: VBO (Vertebrate Breed Ontology)

• Gene: Orthologous genes in other species (with NCBI Gene IDs)

  Search first: NCBI Gene

• Natural Disease:
• Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
• Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
• Comparative Biology:
• Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
• Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
• Transmission (if applicable):
• Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
• Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

• Model Types:
• Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
• Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
• Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
• Genetic Models:
• Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
• Model Characteristics:
• Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
• Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
• Applications:
• Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
• Resources:
• Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

• Cite primary literature (PMID preferred) for all mechanistic and clinical claims
• Prioritize recent reviews and landmark papers
• Include direct quotes from abstracts where possible to support key statements
• Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, NCIT, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (NCIT terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Autosomal Recessive Nonsyndromic Hearing Loss 79 (DFNB79; TPRN-related)

Executive summary

DFNB79 is an extremely rare Mendelian form of isolated sensorineural hearing loss caused by biallelic pathogenic variants in TPRN (formerly C9orf75), which encodes the stereociliary protein taperin. The strongest human evidence comes from consanguineous families with prelingual, bilateral, severe-to-profound hearing loss and no reported vestibular or extra-auditory manifestations. Experimental evidence places taperin at the taper/base of cochlear hair-cell stereocilia, where it participates in organization of the membrane–actin/rootlet apparatus. Loss or mislocalization of taperin disrupts stereocilia, ultimately causing hair-cell dysfunction or degeneration and hearing loss. There is no established DFNB79-specific prevalence, drug, gene therapy, biomarker, natural-history registry, or clinical trial. Current care therefore follows general management for genetic sensorineural hearing loss: early audiologic detection, molecular diagnosis, hearing aids where useful, cochlear-implant assessment for severe-to-profound loss, communication support, and genetic counseling.

Table: This table condenses the highest-confidence findings for TPRN-related DFNB79, separating disease-specific evidence from broader hereditary hearing-loss extrapolation. It is useful for rapid knowledge-base population and for identifying where evidence remains sparse, especially treatment and trial data.

1. Disease information

Definition and identifiers

Preferred name: autosomal recessive nonsyndromic hearing loss 79; DFNB79; TPRN-related nonsyndromic hearing loss. Common historical names include deafness, autosomal recessive 79, nonsyndromic deafness DFNB79, C9orf75-related deafness, and taperin-related hearing loss.

The disease is generally catalogued in OMIM as Deafness, autosomal recessive 79 (DFNB79), OMIM #613307; TPRN is located at 9q34.3. The original study interrogated a 2.9-Mb DFNB79 interval containing 108 candidate genes and established C9orf75/TPRN as causal through linkage, sequencing, segregation, and protein-localization evidence (rehman2010targetedcaptureand pages 3-4, rehman2010targetedcaptureand pages 6-7, rehman2010targetedcaptureand pages 1-3). A disease-specific Orphanet, ICD-10, ICD-11, or MeSH code was not identified in the retrieved literature; clinically it is coded under broader congenital or sensorineural hearing-loss categories. A precise MONDO identifier could not be verified from the retrieved evidence and should be resolved directly against the current MONDO release rather than inferred.

Evidence provenance: the clinical description is aggregated from research pedigrees, not longitudinal EHR-derived population data. The foundational report analyzed four consanguineous Pakistani families—PKDF741, PKDF517, PKDF280, and PKDF1129 (rehman2010targetedcaptureand pages 5-6, rehman2010targetedcaptureand pages 1-3).

2. Etiology

Causal factor

DFNB79 is a germline, autosomal-recessive loss-of-function disorder. Disease results when an individual inherits pathogenic TPRN alleles on both homologues. The discovery variants were one nonsense and three frameshifting alleles, strongly supporting loss of functional taperin rather than gain of function (rehman2010targetedcaptureand pages 5-6, rehman2010targetedcaptureand pages 8-10).

Risk factors

• Genetic: biallelic pathogenic/likely pathogenic TPRN variants; parental carrier status; family history compatible with recessive deafness; and parental relatedness, which increases homozygosity for rare alleles. The original families were consanguineous (rehman2010targetedcaptureand pages 1-3).
• Population context: consanguinity increases the burden and discovery rate of autosomal-recessive nonsyndromic hearing loss generally. A 2024 review reported that individual rarer genes each account for less than 2% of profound hearing-loss cases in studied Pakistani cohorts, but it did not provide a TPRN-specific estimate.
• Environmental, infectious, lifestyle, age, and sex risks: none are established as causes of DFNB79. Noise, aminoglycosides, cisplatin, meningitis, congenital CMV, and other exposures can independently worsen hearing but should not be represented as causes of the Mendelian disorder.

Protective factors and gene–environment interaction

No protective TPRN allele, modifier gene, diet, medication, or validated environmental intervention has been demonstrated. No DFNB79-specific gene–environment interaction has been established. Avoidance of excessive noise and ototoxic exposures is prudent hearing-conservation practice, but evidence that it changes the TPRN-specific natural history is absent.

3. Phenotypes

Core phenotype

The best-supported phenotype is bilateral, prelingual, severe-to-profound sensorineural hearing loss. Vestibular function was described as normal, and no consistent syndromic manifestations were reported in the original families (rehman2010targetedcaptureand pages 6-7, rehman2010targetedcaptureand pages 1-3).

Suggested phenotype annotations are:

• Sensorineural hearing impairment — HP:0000407; clinical sign, bilateral and cochlear.
• Bilateral sensorineural hearing impairment — HP:0008619 where accepted by the target HPO release.
• Severe hearing impairment — HP:0012713 and/or profound hearing impairment — HP:0012714.
• Prelingual hearing loss — HP:0012717.
• Congenital hearing impairment — HP:0008527 only when objectively documented at birth; “prelingual” should not automatically be converted to “congenital.”
• Progressive hearing impairment — HP:0001730 for patients/families with serially demonstrated progression. Progression is reported in some TPRN literature, but it should not be assigned universally because the discovery cohort was already severely affected before speech acquisition.
• Normal vestibular function is a negative finding, not an HPO disease feature.

Published case numbers are too small to calculate defensible phenotype percentages, penetrance, or genotype–phenotype correlations. There is no well-defined behavioral, biochemical, hematologic, imaging, or systemic laboratory phenotype.

Functional and quality-of-life effects

Disease-specific patient-reported outcome data are unavailable. By extrapolation from congenital childhood hearing loss, delayed access to sound can affect spoken-language acquisition, education, social participation, cognition, and well-being. A 2023 review summarized consequences as impairment of “verbal communication, linguistic skills, educational progress, social integration, cognitive aptitude, and overall well-being.” These are general hearing-loss effects, not uniquely measured in DFNB79.

4. Genetic and molecular information

Gene and protein

• Gene: TPRN; historical symbol C9orf75.
• Locus: chromosome 9q34.3.
• Product: taperin, a protein concentrated at the taper/base of inner- and outer-hair-cell stereocilia.
• Gene architecture: the initially described open reading frame extended across four exons and encoded a 711-amino-acid protein; exon 1 encoded most of the protein. Human and mouse taperin showed approximately 68% identity and 75% similarity in the original comparison (rehman2010targetedcaptureand pages 5-6).

Transcript and protein lengths vary by reference isoform; consequently, clinical laboratories must report the exact transcript and genome build.

Landmark pathogenic variants

Rehman et al. reported four exon-1 truncating variants:

1. c.1056G>A, p.Trp352Ter (originally p.W352X), family PKDF741;
2. c.1244delC, family PKDF517;
3. c.44_54dup, family PKDF280;
4. c.42_52del, family PKDF1129.

The variants cosegregated with hearing loss and were absent from approximately 488–500 Pakistani control chromosomes and 400 Coriell control chromosomes tested at the time (rehman2010targetedcaptureand pages 5-6, rehman2010targetedcaptureand pages 8-10). They are germline variants. Frameshift/nonsense alleles are expected to produce nonsense-mediated decay or truncated protein, but transcript-specific NMD must be evaluated variant by variant.

These historical observations do not substitute for contemporary ACMG/AMP classification. Current classification should incorporate ClinVar assertions, segregation, phenotype specificity, predicted NMD, and current ancestry-matched gnomAD frequencies. No reliable current allele frequencies were available in the retrieved evidence; rarity should therefore be queried directly in the current gnomAD release. VUS must not be used alone for diagnosis or reproductive decision-making.

Modifiers, epigenetics, and structural variation

No human modifier gene or epigenetic lesion has been validated. Experimental interaction with GRXCR2, CLIC5, RDX, MYO6, PTPRQ, and related stereociliary-base proteins defines a functional network, not proven human modifiers. No recurrent TPRN deletion, inversion, translocation, aneuploidy, methylation signature, somatic mutation, or repeat expansion is established.

5. Environmental information

DFNB79 is not an infectious, toxic, nutritional, occupational, or lifestyle-induced condition. There is no evidence that smoking, alcohol, exercise, or diet alters penetrance. Acquired causes of hearing loss—congenital CMV, meningitis, hypoxia, noise, aminoglycosides, platinum chemotherapy, and trauma—remain relevant differential or additive insults. They should be separately captured rather than merged into TPRN etiology.

6. Mechanism and pathophysiology

Ordered causal chain

1. Biallelic TPRN loss-of-function variants lead to absent, reduced, or truncated taperin.
2. Deficient taperin leads to failure of normal protein organization at the taper/base of cochlear hair-cell stereocilia; this step is demonstrated mainly in mouse and cellular systems and inferred in human DFNB79.
3. Disruption of the taperin-associated CLIC5–radixin–MYO6–PTPRQ/GRXCR2 membrane–actin complex leads to abnormal anchoring and regulation of stereociliary F-actin at the taper/rootlet region (liu2018grxcr2regulatestaperin pages 1-3, li2021nterminusofgrxcr2 pages 8-9).
4. Abnormal taper/rootlet organization leads to malformed, elongated, disorganized, or progressively degenerating stereocilia and reduced mechanical stability (liu2018grxcr2regulatestaperin pages 1-3, liu2018grxcr2regulatestaperin pages 10-12).
5. Stereociliary structural failure leads to impaired hair-bundle mechanotransduction and, with progression, hair-cell degeneration; direct TPRN-human temporal evidence is limited.
6. Hair-cell dysfunction/loss leads to bilateral cochlear sensorineural hearing loss.

Mechanistic detail

Taperin is enriched at the stereociliary base, near the pointed ends of parallel actin filaments. The discovery study noted limited homology to phostensin and proposed regulation of actin dynamics, but that biochemical role was initially hypothetical (rehman2010targetedcaptureand pages 8-10). Later mouse work demonstrated that GRXCR2 restricts taperin to the base. In Grxcr2-deficient hair cells, taperin spreads along stereocilia, which become elongated and disorganized; reducing Tprn dosage rescues morphology and improves hearing. This is unusually strong genetic evidence that both taperin abundance and spatial restriction matter (liu2018grxcr2regulatestaperin pages 1-3, liu2018grxcr2regulatestaperin pages 10-12).

CLIC5 is cytoskeleton-associated at this site and forms a functional complex with radixin, taperin, and myosin VI. GRXCR2 also interacts with CLIC5; loss of either protein causes disorganized bundles and diffuse taperin localization (li2021nterminusofgrxcr2 pages 8-9). These data favor a structural/cytoskeletal mechanism over a canonical signaling-cascade, metabolic, inflammatory, or immune mechanism.

No reproducible DFNB79-specific abnormalities have been reported for Wnt, MAPK, PI3K–AKT, mTOR, autophagy, metabolism, immune activation, DNA methylation, lipidomics, or circulating proteomics. No human single-cell, spatial-transcriptomic, metabolomic, or multi-omic DFNB79 profile was identified.

Suggested GO terms: stereocilium organization (GO:0032429), actin filament organization (GO:0007015), actin cytoskeleton organization (GO:0030036), sensory perception of sound (GO:0007605), inner-ear receptor-cell stereocilium organization, and mechanosensory behavior where supported. Suggested cellular components include stereocilium (GO:0032420), stereocilium base, actin cytoskeleton (GO:0015629), and cuticular plate.

Suggested Cell Ontology terms: inner hair cell (CL:0000589, verify current release), outer hair cell (CL:0000601, verify current release), and auditory hair cell/sensory epithelial cell. The main upstream lesion is molecular/cytoskeletal; stereocilia degeneration, mechanotransduction failure, and hair-cell loss are downstream.

7. Anatomical structures affected

• Organ/system: inner ear, principally the cochlea and auditory system.
• Anatomical site: organ of Corti/cochlear sensory epithelium; suggested UBERON:0001844 (cochlea) and the current UBERON term for organ of Corti.
• Cells: inner and outer cochlear hair cells.
• Subcellular site: actin-rich stereocilia, particularly their taper/base and rootlet-associated membrane–cytoskeleton interface; cuticular plate involvement is downstream.
• Laterality: bilateral in reported patients.
• Secondary organs: none consistently involved. Normal reported vestibular function argues against routine labeling as vestibular disease, although formal testing remains reasonable when symptoms occur (rehman2010targetedcaptureand pages 1-3).

8. Temporal development

Human onset is usually prelingual; some reports describe progressive TPRN-associated hearing loss. The sparse literature supports a spectrum from early severe/profound loss to progressive deterioration rather than a rigorously defined stage system. The course is chronic and lifelong without auditory rehabilitation; spontaneous remission is not expected. Mouse evidence indicates progressive stereocilia and hair-cell pathology after development, supporting biologic plausibility for human progression (liu2018grxcr2regulatestaperin pages 10-12).

The critical clinical period is early childhood, when auditory access strongly influences language development. This supports prompt diagnostic audiology, amplification, cochlear-implant assessment, and communication intervention, but no TPRN-specific therapeutic window has been established.

9. Inheritance and population

Inheritance is autosomal recessive. For two confirmed heterozygous carrier parents, each pregnancy has a 25% probability of an affected child, 50% probability of a carrier, and 25% probability of inheriting neither familial allele. Males and females are expected to be affected equally.

Penetrance appears high for biallelic truncating alleles in reported pedigrees, but the sample is insufficient to claim complete penetrance. Expressivity includes variation in onset/progression and severity. Anticipation is not expected; germline mosaicism has not been specifically reported but remains a general residual counseling consideration.

The original evidence was enriched in Pakistani and North African/Moroccan consanguineous families, reflecting ascertainment and recessive mapping rather than proof of ancestry restriction. No global prevalence, incidence, sex ratio, carrier frequency, or robust founder-effect estimate exists for DFNB79. Broader congenital hearing loss occurs in approximately 1–3 per 1,000 births, and 2024 reviews estimate that 50–70% or more has a genetic basis; these figures must not be entered as DFNB79 prevalence (yun2024updatesongenetic pages 1-2, brotto2024autosomalrecessivenonsyndromic pages 1-2, lee2024clinicalgenetictesting pages 1-2).

10. Diagnostics

Clinical evaluation

Diagnosis begins with age-appropriate behavioral audiometry and objective testing: otoacoustic emissions, tympanometry, auditory brainstem response, and frequency-specific thresholds. Findings should establish bilateral sensorineural rather than conductive loss. Vestibular assessment is symptom-directed. CT or MRI is not diagnostic of DFNB79 but may be used before cochlear implantation or where anatomic/auditory-nerve abnormalities are suspected. There is no blood chemistry, enzyme assay, biopsy, histopathology, or circulating biomarker for DFNB79.

Molecular testing strategy

1. Use a comprehensive hearing-loss multigene panel including TPRN, sequencing plus exon-level CNV analysis.
2. If negative, consider exome or genome sequencing with CNV/structural-variant and mitochondrial analysis, followed by periodic reanalysis.
3. In a family with known TPRN variants, use targeted familial testing for segregation, carrier testing, prenatal diagnosis, or preimplantation genetic testing.
4. Confirm phase: two variants must be shown or strongly inferred to be in trans.

Contemporary panels have an approximately 40% diagnostic yield across heterogeneous hearing-loss cohorts—not specifically DFNB79. Whole-genome sequencing can detect noncoding and structural variants missed by conventional panel/exome analysis (yun2024updatesongenetic pages 1-2, lee2024clinicalgenetictesting pages 1-2). CMA, karyotyping, FISH, repeat-expansion testing, and isolated mitochondrial testing are not first-line tests for a classic biallelic TPRN phenotype unless other findings indicate them.

Differential diagnosis

The differential encompasses other recessive nonsyndromic hearing-loss genes, especially GJB2/GJB6, STRC, OTOF, SLC26A4, TMC1, TMPRSS3, MYO15A, CDH23, and many others; syndromic disorders such as Usher, Pendred, Alport, and mitochondrial disease; congenital CMV; auditory neuropathy; structural inner-ear anomalies; and acquired ototoxic/noise injury. A broad panel is preferable to phenotype-only single-gene guessing because more than 148–150 nonsyndromic hearing-loss genes are now recognized (yun2024updatesongenetic pages 1-2, lee2024clinicalgenetictesting pages 1-2).

Screening

Universal newborn hearing screening can identify early bilateral loss but does not identify TPRN etiology. Cascade testing is appropriate after a molecular diagnosis. Population-wide TPRN carrier screening is not currently evidence-based, although nonsyndromic hearing-loss genes are increasingly debated for reproductive carrier panels.

11. Outcome and prognosis

DFNB79 is not known to shorten life expectancy or cause disease-specific mortality. Its burden is auditory disability rather than systemic organ failure. Untreated severe/profound prelingual loss can substantially affect speech, education, social participation, and employment, but outcomes vary with communication modality, timing of intervention, family support, and access to services.

There are no TPRN-specific survival curves, quality-of-life scores, prognostic biomarkers, or validated prediction models. Residual hearing, progression rate, age at intervention, auditory-nerve integrity, and consistent rehabilitation are clinically relevant general prognostic factors. Because TPRN pathology is localized to sensory hair-cell stereocilia rather than known primary spiral-ganglion disease, cochlear implantation is mechanistically plausible; however, no adequately sized TPRN-specific outcome series was retrieved.

12. Treatment

Current management

There is no approved disease-modifying pharmacotherapy for TPRN-related hearing loss. Management is individualized:

• hearing aids for aidable residual hearing;
• cochlear-implant evaluation for bilateral severe-to-profound loss with insufficient aided benefit;
• speech-language/auditory rehabilitation where spoken-language goals are chosen;
• sign-language and multimodal communication access;
• educational accommodations and psychosocial support;
• serial audiometry where progression is possible.

Suggested NCIT intervention concepts include Hearing Aid, Cochlear Implantation, Speech and Language Therapy, Audiologic Rehabilitation, and Genetic Counseling; exact NCIT identifiers should be resolved against the deployed NCIT version.

No TPRN-specific response rate or adverse-event series exists. General cochlear-implant evidence in genetic hearing loss suggests sensory/non-neural cochlear disorders often perform at or above cohort medians, but extrapolation to DFNB79 remains indirect.

Experimental therapies and 2023–2024 context

As of the searched evidence, there was no TPRN-specific human gene-replacement, editing, RNA, cell-therapy, or drug trial. A 2024 review identified 17 preclinical and three clinical AAV programs across autosomal-recessive deafness, but the clinical programs targeted OTOF/DFNB9, not TPRN (brotto2024autosomalrecessivenonsyndromic pages 1-2, brotto2024autosomalrecessivenonsyndromic pages 3-5). Relevant OTOF trials included NCT05788536, NCT05821959, and NCT05901480; their results cannot be attributed to DFNB79.

The field nonetheless provides proof of concept. A 2024 bilateral OTOF study treated five children: all showed bilateral hearing restoration, with ABR thresholds improving from greater than 95 dB at baseline to approximately 50–85 dB at follow-up; no dose-limiting toxicity or serious adverse event occurred. This is encouraging for inner-ear gene therapy generally but is gene-, cell-, vector-, and timing-specific and does not demonstrate TPRN efficacy. Reviews emphasize that precision strategies are required because target-cell transduction and therapeutic windows differ across genes (yun2024updatesongenetic pages 1-2, duhon2024genetherapyadvancements pages 20-21, brotto2024autosomalrecessivenonsyndromic pages 3-5).

13. Prevention

The occurrence of a de novo inherited Mendelian allele cannot be prevented by lifestyle modification or vaccination.

• Primary/reproductive: nondirective genetic counseling, partner testing, cascade carrier testing, preimplantation genetic testing, prenatal diagnosis, donor gametes, or natural conception with testing according to family values.
• Secondary: universal newborn hearing screening, prompt diagnostic ABR/audiology, and early molecular testing.
• Tertiary: amplification or implantation, communication access, rehabilitation, educational support, hearing conservation, and avoidance of unnecessary ototoxic exposure.

No vaccine, chemoprophylaxis, diet, or public-health exposure intervention prevents TPRN-related disease. Counseling should respect Deaf-community perspectives; reproductive screening for nonsyndromic hearing loss raises ethical concerns about disability framing and informed choice.

14. Other species and natural disease

The experimentally important ortholog is Tprn in the laboratory mouse, Mus musculus (NCBI Taxonomy 10090). Human and mouse proteins are substantially conserved, and the loci are syntenic (rehman2010targetedcaptureand pages 5-6). No well-established naturally occurring TPRN-associated veterinary disease or breed predisposition was identified. The condition is not transmissible or zoonotic.

15. Model organisms

Mouse models

Tprn-null/knockout mice are the principal disease models. They recapitulate progressive hearing loss, abnormal stereociliary taper/rootlet architecture, bundle degeneration, and subsequent hair-cell loss. These models support the causal sequence from taperin deficiency to structural hair-bundle failure and auditory dysfunction (liu2018grxcr2regulatestaperin pages 10-12).

Grxcr2-deficient mice provide a complementary pathway model: taperin is present but mislocalized along stereocilia, causing elongation and disorganization. Reduction of one Tprn allele substantially rescues stereocilia morphology and hearing, demonstrating a dosage-sensitive genetic interaction (liu2018grxcr2regulatestaperin pages 1-3, liu2018grxcr2regulatestaperin pages 10-12). Clic5-deficient models similarly disrupt the taperin/radixin/MYO6 complex and stereociliary-base organization (li2021nterminusofgrxcr2 pages 8-9).

Applications: defining stereociliary-base architecture, testing actin regulation, identifying therapeutic windows, evaluating hair-cell-targeted vectors, and distinguishing loss from mislocalization toxicity. Limitations: mouse cochlear maturation and auditory frequencies differ from humans; complete knockout may not model every hypomorphic allele; and rescue of developmental mouse pathology does not establish safety or efficacy in older human cochleae.

No validated TPRN patient iPSC, organoid, zebrafish, rat, Drosophila, or naturally occurring large-animal model was identified in the retrieved corpus.

Recent-development assessment and evidence limitations

The key 2023–2024 advances were primarily field-wide: broader clinical use of hearing-loss panels, increasing consideration of genome sequencing, and first-in-human successes for OTOF gene therapy. A June 2024 review stated that panels provide “comprehensive genetic testing,” while an April 2024 review emphasized that genome sequencing can detect “both noncoding and structural variations” (yun2024updatesongenetic pages 1-2, lee2024clinicalgenetictesting pages 1-2). These advances improve DFNB79 diagnosis and establish a translational roadmap, but they do not yet constitute TPRN-directed therapy.

A late-2024 paper titled Critical role of TPRN rings in the stereocilia for hearing was located bibliographically (Molecular Therapy; DOI: https://doi.org/10.1016/j.ymthe.2024.12.004), but its full evidence could not be retrieved in the available corpus. Its detailed quantitative claims are therefore not incorporated as established evidence here. Likewise, the second 2010 AJHG report (DOI: https://doi.org/10.1016/j.ajhg.2010.02.003) and a 2013 Pakistani-family report (DOI: https://doi.org/10.1007/s10528-013-9568-y) were bibliographically identified but not sufficiently accessible for exact case-level extraction. This report consequently relies most heavily on the directly retrieved Rehman et al. discovery study and later mechanistic papers.

Key references

1. Rehman AU et al. Targeted capture and next-generation sequencing identifies C9orf75, encoding taperin, as the mutated gene in nonsyndromic deafness DFNB79. American Journal of Human Genetics. March 2010;86:378–388. DOI: https://doi.org/10.1016/j.ajhg.2010.01.030. The study identified “four distinct truncating mutations” and localized taperin to the stereociliary taper region (rehman2010targetedcaptureand pages 5-6, rehman2010targetedcaptureand pages 1-3).
2. Liu C et al. GRXCR2 regulates taperin localization critical for stereocilia morphology and hearing. Cell Reports. October 2018;25:1268–1280.e4. DOI: https://doi.org/10.1016/j.celrep.2018.09.063 (liu2018grxcr2regulatestaperin pages 1-3, liu2018grxcr2regulatestaperin pages 10-12).
3. Li J et al. N-Terminus of GRXCR2 interacts with CLIC5 and is essential for auditory perception. Frontiers in Cell and Developmental Biology. May 2021. DOI: https://doi.org/10.3389/fcell.2021.671364 (li2021nterminusofgrxcr2 pages 8-9).
4. Yun Y, Lee S-Y. Updates on Genetic Hearing Loss: From Diagnosis to Targeted Therapies. Journal of Audiology and Otology. April 2024;28:88–92. DOI: https://doi.org/10.7874/jao.2024.00157 (yun2024updatesongenetic pages 1-2).
5. Brotto D et al. Autosomal Recessive Non-Syndromic Deafness: Is AAV Gene Therapy a Real Chance? Audiology Research. February 2024;14:239–253. DOI: https://doi.org/10.3390/audiolres14020022 (brotto2024autosomalrecessivenonsyndromic pages 1-2, brotto2024autosomalrecessivenonsyndromic pages 3-5).
6. Lee NK et al. Clinical Genetic Testing for Hearing Loss: Implications for Genetic Counseling and Gene-Based Therapies. Biomedicines. June 2024;12:1427. DOI: https://doi.org/10.3390/biomedicines12071427 (lee2024clinicalgenetictesting pages 1-2, lee2024clinicalgenetictesting pages 9-11).

References

1. (rehman2010targetedcaptureand pages 5-6): Atteeq Ur Rehman, Robert J. Morell, Inna A. Belyantseva, Shahid Y. Khan, Erich T. Boger, Mohsin Shahzad, Zubair M. Ahmed, Saima Riazuddin, Shaheen N. Khan, Sheikh Riazuddin, and Thomas B. Friedman. Targeted capture and next-generation sequencing identifies c9orf75, encoding taperin, as the mutated gene in nonsyndromic deafness dfnb79. American journal of human genetics, 86 3:378-88, Mar 2010. URL: https://doi.org/10.1016/j.ajhg.2010.01.030, doi:10.1016/j.ajhg.2010.01.030. This article has 148 citations and is from a highest quality peer-reviewed journal.

2. (rehman2010targetedcaptureand pages 1-3): Atteeq Ur Rehman, Robert J. Morell, Inna A. Belyantseva, Shahid Y. Khan, Erich T. Boger, Mohsin Shahzad, Zubair M. Ahmed, Saima Riazuddin, Shaheen N. Khan, Sheikh Riazuddin, and Thomas B. Friedman. Targeted capture and next-generation sequencing identifies c9orf75, encoding taperin, as the mutated gene in nonsyndromic deafness dfnb79. American journal of human genetics, 86 3:378-88, Mar 2010. URL: https://doi.org/10.1016/j.ajhg.2010.01.030, doi:10.1016/j.ajhg.2010.01.030. This article has 148 citations and is from a highest quality peer-reviewed journal.

3. (rehman2010targetedcaptureand pages 6-7): Atteeq Ur Rehman, Robert J. Morell, Inna A. Belyantseva, Shahid Y. Khan, Erich T. Boger, Mohsin Shahzad, Zubair M. Ahmed, Saima Riazuddin, Shaheen N. Khan, Sheikh Riazuddin, and Thomas B. Friedman. Targeted capture and next-generation sequencing identifies c9orf75, encoding taperin, as the mutated gene in nonsyndromic deafness dfnb79. American journal of human genetics, 86 3:378-88, Mar 2010. URL: https://doi.org/10.1016/j.ajhg.2010.01.030, doi:10.1016/j.ajhg.2010.01.030. This article has 148 citations and is from a highest quality peer-reviewed journal.

4. (rehman2010targetedcaptureand pages 8-10): Atteeq Ur Rehman, Robert J. Morell, Inna A. Belyantseva, Shahid Y. Khan, Erich T. Boger, Mohsin Shahzad, Zubair M. Ahmed, Saima Riazuddin, Shaheen N. Khan, Sheikh Riazuddin, and Thomas B. Friedman. Targeted capture and next-generation sequencing identifies c9orf75, encoding taperin, as the mutated gene in nonsyndromic deafness dfnb79. American journal of human genetics, 86 3:378-88, Mar 2010. URL: https://doi.org/10.1016/j.ajhg.2010.01.030, doi:10.1016/j.ajhg.2010.01.030. This article has 148 citations and is from a highest quality peer-reviewed journal.

5. (liu2018grxcr2regulatestaperin pages 1-3): Chang Liu, Na Luo, Chun-Yu Tung, Benjamin J. Perrin, and Bo Zhao. Grxcr2 regulates taperin localization critical for stereocilia morphology and hearing. Cell reports, 25:1268-1280.e4, Oct 2018. URL: https://doi.org/10.1016/j.celrep.2018.09.063, doi:10.1016/j.celrep.2018.09.063. This article has 32 citations and is from a highest quality peer-reviewed journal.

6. (liu2018grxcr2regulatestaperin pages 10-12): Chang Liu, Na Luo, Chun-Yu Tung, Benjamin J. Perrin, and Bo Zhao. Grxcr2 regulates taperin localization critical for stereocilia morphology and hearing. Cell reports, 25:1268-1280.e4, Oct 2018. URL: https://doi.org/10.1016/j.celrep.2018.09.063, doi:10.1016/j.celrep.2018.09.063. This article has 32 citations and is from a highest quality peer-reviewed journal.

7. (li2021nterminusofgrxcr2 pages 8-9): Jinan Li, Chang Liu, and Bo Zhao. N-terminus of grxcr2 interacts with clic5 and is essential for auditory perception. Frontiers in Cell and Developmental Biology, May 2021. URL: https://doi.org/10.3389/fcell.2021.671364, doi:10.3389/fcell.2021.671364. This article has 12 citations.

8. (yun2024updatesongenetic pages 1-2): Yejin Yun and Sang-Yeon Lee. Updates on genetic hearing loss: from diagnosis to targeted therapies. Journal of Audiology and Otology, 28:88-92, Apr 2024. URL: https://doi.org/10.7874/jao.2024.00157, doi:10.7874/jao.2024.00157. This article has 7 citations.

9. (brotto2024autosomalrecessivenonsyndromic pages 1-2): Davide Brotto, Marco Greggio, Cosimo De Filippis, and Patrizia Trevisi. Autosomal recessive non-syndromic deafness: is aav gene therapy a real chance? Audiology Research, 14:239-253, Feb 2024. URL: https://doi.org/10.3390/audiolres14020022, doi:10.3390/audiolres14020022. This article has 8 citations.

10. (lee2024clinicalgenetictesting pages 1-2): Nam K. Lee, Kristin M. Uhler, Patricia J. Yoon, and Regie Lyn P. Santos-Cortez. Clinical genetic testing for hearing loss: implications for genetic counseling and gene-based therapies. Biomedicines, 12:1427, Jun 2024. URL: https://doi.org/10.3390/biomedicines12071427, doi:10.3390/biomedicines12071427. This article has 6 citations.

11. (lee2024clinicalgenetictesting pages 9-11): Nam K. Lee, Kristin M. Uhler, Patricia J. Yoon, and Regie Lyn P. Santos-Cortez. Clinical genetic testing for hearing loss: implications for genetic counseling and gene-based therapies. Biomedicines, 12:1427, Jun 2024. URL: https://doi.org/10.3390/biomedicines12071427, doi:10.3390/biomedicines12071427. This article has 6 citations.

12. (duhon2024genetherapyadvancements pages 20-21): Bailey H. Duhon, Eric C. Bielefeld, Yin Ren, and Jerusha Naidoo. Gene therapy advancements for the treatment of acquired and hereditary hearing loss. Frontiers in Audiology and Otology, Jul 2024. URL: https://doi.org/10.3389/fauot.2024.1423853, doi:10.3389/fauot.2024.1423853. This article has 9 citations.

13. (brotto2024autosomalrecessivenonsyndromic pages 3-5): Davide Brotto, Marco Greggio, Cosimo De Filippis, and Patrizia Trevisi. Autosomal recessive non-syndromic deafness: is aav gene therapy a real chance? Audiology Research, 14:239-253, Feb 2024. URL: https://doi.org/10.3390/audiolres14020022, doi:10.3390/audiolres14020022. This article has 8 citations.

14. (lee2024clinicalgenetictesting pages 12-13): Nam K. Lee, Kristin M. Uhler, Patricia J. Yoon, and Regie Lyn P. Santos-Cortez. Clinical genetic testing for hearing loss: implications for genetic counseling and gene-based therapies. Biomedicines, 12:1427, Jun 2024. URL: https://doi.org/10.3390/biomedicines12071427, doi:10.3390/biomedicines12071427. This article has 6 citations.

15. (rehman2010targetedcaptureand pages 3-4): Atteeq Ur Rehman, Robert J. Morell, Inna A. Belyantseva, Shahid Y. Khan, Erich T. Boger, Mohsin Shahzad, Zubair M. Ahmed, Saima Riazuddin, Shaheen N. Khan, Sheikh Riazuddin, and Thomas B. Friedman. Targeted capture and next-generation sequencing identifies c9orf75, encoding taperin, as the mutated gene in nonsyndromic deafness dfnb79. American journal of human genetics, 86 3:378-88, Mar 2010. URL: https://doi.org/10.1016/j.ajhg.2010.01.030, doi:10.1016/j.ajhg.2010.01.030. This article has 148 citations and is from a highest quality peer-reviewed journal.

Artifacts

• Edison artifact artifact-00

Reference Validation

Checked with linkml-reference-validator 0.2.1.

All extracted references resolved successfully.

Term Validation

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

Obsolete terms

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

• GO:0032429 (obsolete regulation of phospholipase A2 activity) (1 mention)

15 of 16 terms resolved to a current term; the rest could not be looked up either way.