Autosomal Recessive Nonsyndromic Hearing Loss 26 (DFNB26): Disease-Characteristics Report

Executive summary and evidence limits

DFNB26 is an exceptionally rare Mendelian form of prelingual, bilateral, severe-to-profound sensorineural hearing loss. Current evidence is centered on one large consanguineous Pakistani pedigree, PK-2. The disease allele is homozygous GAB1 c.347G>A, p.(Gly116Glu), a hypomorphic missense substitution in the pleckstrin-homology domain. A second locus, DFNM1, contains a dominant METTL13 c.1631G>A, p.(Arg544Gln) modifier that can suppress deafness in individuals homozygous for the GAB1 allele. Consequently, penetrance cannot be interpreted from GAB1 genotype alone in this family. Functional support comes from biochemical and cell assays, patient lymphoblastoid cells, zebrafish perturbation/rescue, mouse inner-ear localization, and more recent mouse cochlear single-cell data—not from a disease-specific mammalian knock-in model. (yousaf2018modifiervariantof pages 1-3, yousaf2018modifiervariantof pages 8-10, yousaf2018modifiervariantof pages 7-8, yousaf2018modifiervariantof pages 3-4)

Table: Compact summary of the human genetic, modifier, mechanistic, and model-system evidence for GAB1-related DFNB26. It distinguishes demonstrated findings from pathway-level inference and highlights the major knowledge gaps.

Evidence caveat. No replicated unrelated DFNB26 families, disease-specific prevalence estimate, prospective natural-history cohort, or targeted clinical trial was identified. Many requested database fields therefore remain unknown rather than negative.

1. Disease information

Definition

DFNB26 is an autosomal-recessive, nonsyndromic auditory disorder caused by biallelic pathogenic variation in GAB1, encoding GRB2-associated binding protein 1. The reported phenotype is prelingual, bilateral, severe-to-profound or profound sensorineural deafness without recognized extra-auditory manifestations. An authoritative growth-factor review describes GAB1 as a mediator of HGF and IGF1 signaling and lists the DFNB26 phenotype as “prelingual, bilateral, sensorineural, and profound.” (yousaf2018modifiervariantof pages 7-8, naz2020growthfactorand pages 21-23)

Identifiers and synonyms

• Preferred name: autosomal recessive nonsyndromic hearing loss 26.
• Synonyms: DFNB26; deafness, autosomal recessive 26; GAB1-related nonsyndromic hearing loss; GAB1-associated profound deafness.
• Locus: chromosome 4q31, initially delimited to approximately 1.5 cM.
• OMIM: DFNB26 is commonly catalogued as OMIM #605428; GAB1 is OMIM *604439. These identifiers should be verified against the live OMIM record before automated ingestion because OMIM was not directly available through the retrieval interface.
• MONDO: no confidently verified DFNB26-specific MONDO identifier was retrieved. The broader parent “hearing loss, autosomal recessive” is MONDO:0019588, but it is not equivalent to DFNB26. Open Targets did not return a specific GAB1–DFNB26 record in its top results, illustrating incomplete aggregation for this ultra-rare disorder. (OpenTargets Search: autosomal recessive nonsyndromic hearing loss 26)
• Orphanet: no disease-specific Orpha code was verified.
• ICD-10-CM: no genotype-specific code; phenotype may be represented under H90.3, sensorineural hearing loss, bilateral.
• ICD-11/MeSH: use the relevant nonsyndromic/genetic sensorineural hearing-loss parent concept; no DFNB26-specific code was verified.

The evidence is principally family-level research data, not EHR-derived surveillance or an aggregated population registry. Whole-exome sequencing included six deaf relatives from six sibships, one normal-hearing nonpenetrant relative, and an unrelated normal control. (yousaf2018modifiervariantof pages 3-4)

2. Etiology, risk, protection, and gene–environment interaction

Causal factor

The only reported disease allele is germline homozygous GAB1 NM_207123:c.347G>A, p.(Gly116Glu). It affects a conserved residue in the GAB1 pleckstrin-homology domain and was absent from the examined Pakistani/Indian controls and from 1000 Genomes, NHLBI-ESP, and ExAC. Eight computational predictors called it damaging, while lipid-binding and zebrafish experiments supported a partial-loss-of-function, or hypomorphic, effect. (yousaf2018modifiervariantof pages 7-8, yousaf2018modifiervariantof pages 3-4)

Genetic risk and protection

• Primary risk: inheritance of two GAB1 p.Gly116Glu alleles.
• Family history/consanguinity: recessive inheritance makes parental relatedness a major ascertainment factor. The discovery family was consanguineous.
• Protective modifier: heterozygous METTL13 c.1631G>A, p.(Arg544Gln) at DFNM1 behaved as a dominant suppressor. Normal-hearing relatives could be homozygous for GAB1 p.Gly116Glu if they carried this modifier; affected GAB1 homozygotes lacked it. Functional zebrafish rescue supported suppression. (yousaf2018modifiervariantof pages 1-3, yousaf2018modifiervariantof pages 8-10, yousaf2018modifiervariantof pages 3-4)
• Nomenclature caution: one extracted passage gave METTL13 c.1634G>A, but the primary sequence-level result was c.1631G>A/p.Arg544Gln. Transcript and genome-build normalization should precede database loading. (yousaf2018modifiervariantof pages 7-8, yousaf2018modifiervariantof pages 3-4)

No other validated susceptibility, protective, or modifier alleles are known specifically for DFNB26. There is no evidence for anticipation.

Environmental factors and interactions

No noise, infection, drug, diet, smoking, alcohol, occupational exposure, or other environmental factor has been shown to cause or modify DFNB26. General ototoxic exposures may add acquired injury to genetically impaired hearing, but this is clinical precaution rather than a demonstrated DFNB26 gene–environment interaction. No infectious etiology applies.

3. Phenotypes

The hearing phenotype is described as severe-to-profound in the primary investigation and as profound in later summaries. Frequencies cannot be estimated beyond saying that hearing loss tracked GAB1 homozygosity in relatives lacking the suppressor. Exact audiograms, vestibular measurements, longitudinal progression, tinnitus, and quantitative speech outcomes were not available. (yousaf2018modifiervariantof pages 7-8, naz2020growthfactorand pages 21-23)

Quality of life. Disease-specific EQ-5D, SF-36, PROMIS, or hearing-related quality-of-life measurements have not been reported. Untreated prelingual profound hearing loss can materially affect spoken-language acquisition, education, communication, and social participation, but those generic consequences should not be stored as observed PK-2 outcomes.

4. Genetic and molecular information

• Causal gene: GAB1, GRB2-associated binding protein 1, OMIM *604439; chromosome 4q31. It encodes a cytoplasmic docking/adaptor protein downstream of receptor tyrosine kinases.
• Disease variant: NM_207123:c.347G>A, p.(Gly116Glu), missense, germline, homozygous in affected subjects; functionally characterized as hypomorphic. It lies in the pleckstrin-homology domain, affecting lipid-related membrane recruitment/function. (yousaf2018modifiervariantof pages 7-8, yousaf2018modifiervariantof pages 3-4)
• Modifier gene: METTL13, with c.1631G>A, p.(Arg544Gln) at DFNM1. The allele behaves dominantly as a suppressor rather than as the primary cause of DFNB26. (yousaf2018modifiervariantof pages 1-3, yousaf2018modifiervariantof pages 3-4)
• Population frequency: absent from the historical reference datasets and controls examined in the 2018 study. A contemporary gnomAD allele count/frequency was not retrieved and should be checked directly using a normalized transcript/genome coordinate.
• ACMG/AMP classification: the human segregation and functional evidence support pathogenicity, but a current ClinVar assertion was not verified. For knowledge-base purposes, record the published disease association and functional evidence separately from any unverified ClinVar classification.
• Somatic status: not applicable; this is a constitutional germline disorder.
• Structural variants/chromosomal abnormalities: none demonstrated. The 4q31 linkage interval is not itself a pathogenic copy-number change.
• Epigenetics: no DFNB26-specific methylation, chromatin, histone, or imprinting abnormality is known.

5. Environmental information

DFNB26 is genetically initiated. No toxin, radiation, pollution, occupation, lifestyle behavior, or pathogen has been causally associated with it. Standard hearing-conservation measures—avoiding excessive noise and unnecessary ototoxic medication, vaccination against preventable infections that can damage hearing, and prompt treatment of otitis—may preserve residual auditory function but do not prevent inheritance or reverse GAB1 dysfunction.

6. Mechanism and pathophysiology

Ordered causal chain

1. Homozygous GAB1 p.Gly116Glu alters the pleckstrin-homology domain, which leads to reduced lipid-associated/membrane adaptor function; this hypomorphic effect is experimentally supported. (yousaf2018modifiervariantof pages 7-8, yousaf2018modifiervariantof pages 3-4)
2. Reduced GAB1 function leads to abnormal propagation/regulation of receptor-tyrosine-kinase signals, especially the HGF–MET–GAB1 axis; the pathway placement is established, whereas its exact magnitude in human cochlear cells is inferred. (naz2020growthfactorand pages 21-23, mujtaba2015amutationof pages 4-6)
3. Altered signaling results in dysregulation of downstream effectors. Patient lymphoblastoid cells showed more-than-twofold changes in several HGF/MET-pathway genes and selective SPRY2 upregulation in deaf—but not modifier-protected—GAB1 homozygotes. PI3K was upregulated in both affected and nonpenetrant groups, so PI3K expression alone does not explain penetrance. (yousaf2018modifiervariantof pages 6-7)
4. Branch A—without the METTL13 suppressor: abnormal GAB1–SPRY2 pathway regulation is inferred to lead to impaired development or maintenance of cochlear neural/strial/supporting-cell systems, which results in bilateral severe-to-profound sensorineural hearing loss.
5. Branch B—with METTL13 p.Arg544Gln: altered METTL13 action within a supported GAB1–METTL13–SPRY2 complex leads to normalization or compensation of critical signaling and results in preserved hearing despite GAB1 homozygosity. Human segregation demonstrates suppression, while the precise biochemical corrective step remains unresolved. (yousaf2018modifiervariantof pages 1-3, yousaf2018modifiervariantof pages 8-10, yousaf2018modifiervariantof pages 6-7)

Pathways and cellular processes

Activated MET recruits GAB1/GRB2 and can engage PI3K, PTPN11/SHP2, PTK2, STAT, and RAS–RAF–MAPK/ERK signaling. These pathways regulate proliferation, survival, migration, morphogenesis, and tissue maintenance. Related HGF, MET, GAB1, and MAP3K1 deafness genes reinforce a shared auditory signaling network, but it is not established that every branch is abnormal in DFNB26 cochleae. (faridi2024deafnessdfnb128associated pages 1-2, mujtaba2015amutationof pages 4-6, naz2020growthfactorand pages 5-7)

Suggested terms include GO:0007169 transmembrane receptor protein tyrosine kinase signaling; GO:0008286 insulin receptor signaling pathway, where appropriate for GAB1; GO:0048011 neurotrophin TRK receptor signaling; GO:0043066 negative regulation of apoptotic process; GO:0007165 signal transduction; GO:0048870 cell motility; and GO:0007420 brain development. Exact GAB1 annotations should be drawn from the current GO release rather than inferred wholesale from the pathway.

Cell and anatomical context

Mouse immunolocalization found overlapping Gab1/Mettl13 expression in spiral ganglion neurons, cochlear sensory-neuron fibers, supporting cells, and vestibular/cochlear regions. A 2024 mouse cochlear single-cell/single-nucleus analysis provided newer pathway context: Gab1, Hgf, and Map3k1 were detected in stria-vascularis marginal cells; Met in intermediate cells; pathway components also occurred in spiral ganglion neurons, with little expression in inner or outer hair cells in those datasets. This argues against assuming that DFNB26 is a hair-cell-autonomous disorder. (yousaf2018modifiervariantof pages 6-7, faridi2024deafnessdfnb128associated pages 8-10)

Suggested CL terms: CL:0000210 photoreceptor-like sensory receptor cell is not recommended because it is too broad; use current ontology terms for spiral ganglion neuron, inner-ear supporting cell, stria vascularis marginal cell, and stria vascularis intermediate cell after ontology-browser verification. Suggested processes include neuronal signaling, epithelial morphogenesis, survival, and cochlear ion-homeostasis support.

Molecular profiling and advanced technology

• Transcript/expression: patient lymphoblastoid-cell qPCR/expression comparisons implicated SPRY2 and other HGF/MET components. This is an accessible surrogate tissue, not direct human cochlea. (yousaf2018modifiervariantof pages 6-7)
• Proteomics/interactome: NanoSPD/co-immunoprecipitation and COS-7 assays supported association among GAB1, METTL13, and SPRY2; the disease and modifier substitutions did not simply abolish GAB1–METTL13 binding. (yousaf2018modifiervariantof pages 8-10, yousaf2018modifiervariantof pages 6-7)
• Single-cell: 2024 mouse cochlear data refined likely strial and neuronal cell contexts but did not directly profile DFNB26 tissue. (faridi2024deafnessdfnb128associated pages 8-10)
• Metabolomics/lipidomics/spatial transcriptomics/CRISPR screens: no disease-specific results found.
• Immune, inflammatory, fibrotic, ischemic, or metabolic injury: not demonstrated as central DFNB26 mechanisms.

7. Anatomical structures affected

• Organ/system: bilateral inner ear and auditory system; no demonstrated systemic organ disease.
• Primary site: cochlea (UBERON:0001844).
• Relevant structures: organ of Corti (UBERON:0002227, verify current release), spiral ganglion, stria vascularis, cochlear supporting tissues, and auditory nerve fibers.
• Cellular compartments: cytosol and plasma-membrane-associated signaling regions; GAB1’s PH domain mediates phospholipid-related localization. Suggested GO cellular-component terms include GO:0005737 cytoplasm, GO:0005886 plasma membrane, and receptor-signaling complexes where directly annotated.
• Lateralization: bilateral. No consistent asymmetry has been reported. (naz2020growthfactorand pages 21-23)

8. Temporal development

Onset is prelingual and likely congenital or very early childhood, but a precise birth-to-diagnosis interval was not reported. The available family data do not establish whether thresholds are stable or progressive. The condition should therefore be represented as chronic/lifelong severe auditory impairment, with progression coded unknown, not stable. There are no defined stages, spontaneous remissions, or episodic attacks.

The critical clinical period is early infancy and childhood, when auditory access is required for spoken-language development. Newborn detection, prompt etiologic testing, amplification, communication support, and timely cochlear-implant evaluation are therefore important even though no DFNB26-specific timing trial exists.

9. Inheritance and population

• Inheritance: autosomal recessive at the GAB1 locus, complicated by dominant suppression at METTL13/DFNM1.
• Recurrence risk: if both parents carry the familial GAB1 allele, each pregnancy has a nominal 25% probability of GAB1 homozygosity, 50% carrier probability, and 25% probability of inheriting neither allele. Phenotypic risk may be lower when the protective METTL13 allele segregates; counseling requires joint two-locus analysis.
• Penetrance: incomplete when GAB1 is considered alone; apparently high among homozygotes lacking the modifier in PK-2, but no defensible percentage can be calculated from the extracted data.
• Expressivity: severe-to-profound/profound among affected relatives; broader variability is unknown.
• Anticipation: not expected or reported.
• Germline mosaicism: not reported; standard residual risk applies.
• Founder effect/carrier frequency: unknown. The allele was identified in one Pakistani family and absent from tested regional controls; that is insufficient to establish a founder mutation. (yousaf2018modifiervariantof pages 3-4)
• Sex ratio: no sex bias expected for an autosomal trait; disease-specific ratio unavailable.
• Prevalence/incidence: no cases-per-100,000 or annual incidence estimate exists. A 2024 Pakistani review reported more than 148 hearing-loss genes and 170 loci overall and 51 autosomal-recessive nonsyndromic genes identified in Pakistan; common genes explain over half of profound cases, while individually uncommon genes contribute under 2%. These are background statistics, not DFNB26 prevalence estimates. GAB1 remains an ultra-rare cause. (faridi2024deafnessdfnb128associated pages 1-2)

10. Diagnostics

Clinical evaluation

1. Newborn physiologic screening with otoacoustic emissions and/or automated auditory brainstem response.
2. Diagnostic age-appropriate behavioral audiometry and frequency-specific auditory brainstem response to document bilateral sensorineural thresholds.
3. Tympanometry and otoscopy to exclude conductive disease; speech detection/perception testing when developmentally appropriate.
4. Vestibular assessment only if symptoms or implant planning warrant it; vestibular phenotype is not established.
5. Renal, ophthalmic, cardiac, or other syndromic testing should be driven by clinical findings rather than DFNB26 itself.

No blood chemistry, metabolite, protein biomarker, biopsy, or characteristic imaging sign diagnoses DFNB26. CT/MRI is used for cochlear-implant planning or suspected structural abnormalities, not molecular confirmation.

Genetic testing strategy

• First line: a comprehensive hearing-loss panel that includes GAB1, copy-number analysis, and established differential genes such as GJB2/GJB6, SLC26A4, OTOF, STRC, TMC1, MYO15A, CDH23, TMPRSS3, and ancestry-relevant genes.
• Familial variant testing: targeted sequencing for GAB1 c.347G>A plus METTL13 c.1631G>A when the PK-2-associated alleles or pedigree linkage are relevant.
• Exome/genome sequencing: appropriate after a negative panel, in consanguineous families, or when modifier/digenic architecture is suspected. Segregation analysis is essential; the original discovery required exome sequencing plus linkage and family cosegregation. (yousaf2018modifiervariantof pages 1-3, yousaf2018modifiervariantof pages 3-4)
• WGS: potentially superior for regulatory, intronic, and structural variants, but no DFNB26-specific incremental yield has been quantified.
• CMA/karyotype/FISH/mtDNA/repeat testing: not routine for isolated DFNB26 unless phenotype or family history suggests another diagnosis.
• RNA studies: not standard clinically; lymphoblastoid-cell cDNA confirmed expression of the reported variants in research. (yousaf2018modifiervariantof pages 3-4)

Differential diagnosis

The differential includes other congenital/prelingual AR nonsyndromic hearing losses, auditory neuropathy such as OTOF-related disease, enlarged-vestibular-aqueduct/SLC26A4 disease, congenital CMV, ototoxic exposure, and syndromic disorders whose non-auditory findings emerge later. DFNB26 is distinguished by biallelic pathogenic GAB1 variants with compatible segregation and, where relevant, METTL13 modifier status.

11. Outcome and prognosis

DFNB26 is not known to shorten life expectancy or cause disease-specific mortality. The principal morbidity is lifelong auditory disability and its communication, educational, and psychosocial consequences. Untreated sensory-neural function is not expected to recover spontaneously. Hearing technology can improve auditory access but does not restore normal GAB1 signaling.

No DFNB26-specific survival statistics, disability-adjusted life years, cochlear-implant speech scores, validated prognostic biomarkers, or recovery rates are available. Important practical prognostic variables are age at identification/intervention, hearing level, residual hearing, consistent device use, communication access, educational support, and implant candidacy—not the GAB1 genotype alone. METTL13 status is a biologically compelling penetrance marker but has been demonstrated in only one pedigree.

12. Treatment and real-world implementation

There is no approved GAB1- or METTL13-directed pharmacotherapy, no established pharmacogenomic rule, and no DFNB26-specific gene, RNA, cell, or immune therapy. The clinical-trial search found no relevant interventional DFNB26 trial.

Current care follows pediatric severe-to-profound hearing-loss practice:

• appropriately fitted hearing aids and verification of aided audibility;
• early auditory, speech-language, sign-language, and educational intervention according to family goals;
• remote-microphone and classroom-access technology;
• cochlear implantation when appropriately fitted hearing aids provide insufficient benefit;
• longitudinal audiology and device programming;
• family and psychosocial support.

Suggested NCIT concepts include Hearing Aid Device, Cochlear Implantation, Speech and Language Therapy, Audiologic Rehabilitation, and Genetic Counseling; exact NCIT identifiers should be resolved in the current NCI Thesaurus release.

Experimental HGF delivery has ameliorated chemically induced hearing impairment in rats, and HGF–MET signaling is an attractive pathway, but this neither demonstrates efficacy in DFNB26 nor justifies off-label pathway stimulation. MET signaling is pleiotropic and oncologically important, so nonspecific manipulation could carry substantial risk. (mujtaba2015amutationof pages 6-8, mujtaba2015amutationof pages 4-6)

13. Prevention

• Primary prevention of inherited disease: genetic counseling, partner testing where a familial allele is known, reproductive carrier testing, prenatal diagnosis, and preimplantation genetic testing for monogenic disease. Two-locus counseling should include METTL13 but should not assume complete protection outside PK-2.
• Secondary prevention: universal newborn hearing screening, rapid diagnostic audiology, molecular testing, and cascade testing of relatives.
• Tertiary prevention: early communication access, amplification/implantation, educational accommodations, and avoidance of additional noise or ototoxic injury.
• Vaccination/public health: routine immunization can prevent some acquired infectious hearing losses but does not prevent DFNB26.
• Prophylactic medication: none.

14. Other species and natural disease

No naturally occurring veterinary disorder attributable to an orthologous GAB1 DFNB26 allele was identified. Relevant orthologs include mouse Gab1 (Mus musculus, NCBI Taxon 10090) and zebrafish gab1 (Danio rerio, NCBI Taxon 7955). These systems support evolutionary conservation of developmental and receptor-signaling functions. There is no zoonotic or cross-species transmission because DFNB26 is inherited, not infectious.

15. Model organisms

Zebrafish

Gab1 morpholino perturbation produced developmental phenotypes, and human GAB1/METTL13 mRNA experiments supported the hypomorphic disease allele and suppressor relationship. Coinjection experiments used 1,000 pg GAB1 and 250 pg METTL13 mRNA; suppressor METTL13 partially rescued the GAB1-associated phenotype. This is the strongest whole-organism functional evidence, but a morpholino developmental phenotype is not identical to human isolated deafness, and zebrafish lateral-line/inner-ear biology cannot establish human cochlear penetrance quantitatively. (yousaf2018modifiervariantof pages 8-10, yousaf2018modifiervariantof pages 3-4)

Mouse

Mouse evidence is primarily expression/localization: Gab1 and Mettl13 overlap in spiral ganglion neurons, auditory nerve fibers, supporting cells, and other inner-ear structures. Later single-cell datasets place HGF–MET–GAB1-related components prominently in strial and neuronal populations. No reported Gab1 p.Gly116Glu knock-in mouse directly reproduces DFNB26. (yousaf2018modifiervariantof pages 6-7, faridi2024deafnessdfnb128associated pages 8-10)

Cellular and biochemical systems

Patient lymphoblastoid cells enabled pathway-expression comparisons; COS-7 cells, NanoSPD, co-immunoprecipitation, and filopodial-tip assays supported GAB1–METTL13–SPRY2 interaction; lipid-binding assays supported PH-domain dysfunction. Limitations include non-cochlear cell context and uncertain correspondence between expression changes and auditory-cell physiology. (yousaf2018modifiervariantof pages 8-10, yousaf2018modifiervariantof pages 6-7)

Recent developments and authoritative interpretation

The principal disease-defining study remains Yousaf et al., March 2018, Journal of Clinical Investigation, “Modifier variant of METTL13 suppresses human GAB1-associated profound deafness,” DOI: 10.1172/JCI97350. Its central finding was that a dominant METTL13 allele can suppress a recessive GAB1-associated phenotype, making DFNB26 a particularly clear human example of modified Mendelian penetrance. (yousaf2018modifiervariantof pages 1-3)

Recent 2024 work has refined context rather than changed the causal assignment. Faridi et al., published 27 June 2024, placed GAB1/DFNB26 in a broader HGF–MET–GAB1–MAP3K1 deafness network and used mouse cochlear single-cell data to emphasize strial and spiral-ganglion expression rather than a simple hair-cell-only mechanism: DOI 10.3390/genes15070845. (faridi2024deafnessdfnb128associated pages 1-2, faridi2024deafnessdfnb128associated pages 8-10) A 2024 review of Pakistani AR nonsyndromic hearing loss underscores how consanguineous pedigrees have enabled rare-gene discovery while showing that most individually uncommon genes each explain under 2% of cases; this supports describing DFNB26 as ultra-rare rather than assigning an unsupported prevalence. (faridi2024deafnessdfnb128associated pages 1-2)

Knowledge-base conclusions

1. High-confidence fields: AR inheritance; GAB1; c.347G>A/p.Gly116Glu; prelingual bilateral severe-to-profound sensorineural hearing loss; 4q31; METTL13 p.Arg544Gln suppressor; HGF–MET adaptor-signaling involvement.
2. Moderate-confidence mechanistic fields: PH-domain hypomorphism, SPRY2 dysregulation, and a GAB1–METTL13–SPRY2 regulatory complex.
3. Inference-only fields: exact cochlear lesion, specific affected human cell type, pathway branch that directly causes auditory failure, and degree of protection conferred by METTL13 outside PK-2.
4. Unavailable fields: DFNB26-specific MONDO/Orpha verification, prevalence, incidence, carrier frequency, quantitative penetrance, audiometric progression, quality-of-life scores, treatment-response rates, prognostic biomarkers, natural veterinary disease, and targeted clinical trials.
5. PMID note: the retrieved full-text evidence exposed DOI records but not reliable PMIDs. PMIDs should therefore be resolved through PubMed by DOI before knowledge-base ingestion rather than guessed.

References

1. (yousaf2018modifiervariantof pages 1-3): Rizwan Yousaf, Zubair M. Ahmed, Arnaud P.J. Giese, Robert J. Morell, Ayala Lagziel, Alain Dabdoub, Edward R. Wilcox, Sheikh Riazuddin, Thomas B. Friedman, and Saima Riazuddin. Modifier variant of mettl13 suppresses human gab1–associated profound deafness. Mar 2018. URL: https://doi.org/10.1172/jci97350, doi:10.1172/jci97350. This article has 58 citations and is from a highest quality peer-reviewed journal.

2. (yousaf2018modifiervariantof pages 8-10): Rizwan Yousaf, Zubair M. Ahmed, Arnaud P.J. Giese, Robert J. Morell, Ayala Lagziel, Alain Dabdoub, Edward R. Wilcox, Sheikh Riazuddin, Thomas B. Friedman, and Saima Riazuddin. Modifier variant of mettl13 suppresses human gab1–associated profound deafness. Mar 2018. URL: https://doi.org/10.1172/jci97350, doi:10.1172/jci97350. This article has 58 citations and is from a highest quality peer-reviewed journal.

3. (yousaf2018modifiervariantof pages 7-8): Rizwan Yousaf, Zubair M. Ahmed, Arnaud P.J. Giese, Robert J. Morell, Ayala Lagziel, Alain Dabdoub, Edward R. Wilcox, Sheikh Riazuddin, Thomas B. Friedman, and Saima Riazuddin. Modifier variant of mettl13 suppresses human gab1–associated profound deafness. Mar 2018. URL: https://doi.org/10.1172/jci97350, doi:10.1172/jci97350. This article has 58 citations and is from a highest quality peer-reviewed journal.

4. (yousaf2018modifiervariantof pages 3-4): Rizwan Yousaf, Zubair M. Ahmed, Arnaud P.J. Giese, Robert J. Morell, Ayala Lagziel, Alain Dabdoub, Edward R. Wilcox, Sheikh Riazuddin, Thomas B. Friedman, and Saima Riazuddin. Modifier variant of mettl13 suppresses human gab1–associated profound deafness. Mar 2018. URL: https://doi.org/10.1172/jci97350, doi:10.1172/jci97350. This article has 58 citations and is from a highest quality peer-reviewed journal.

5. (naz2020growthfactorand pages 21-23): Sadaf Naz and Thomas B. Friedman. Growth factor and receptor malfunctions associated with human genetic deafness. Clinical Genetics, 97:138-155, Oct 2020. URL: https://doi.org/10.1111/cge.13641, doi:10.1111/cge.13641. This article has 17 citations and is from a peer-reviewed journal.

6. (yousaf2018modifiervariantof pages 6-7): Rizwan Yousaf, Zubair M. Ahmed, Arnaud P.J. Giese, Robert J. Morell, Ayala Lagziel, Alain Dabdoub, Edward R. Wilcox, Sheikh Riazuddin, Thomas B. Friedman, and Saima Riazuddin. Modifier variant of mettl13 suppresses human gab1–associated profound deafness. Mar 2018. URL: https://doi.org/10.1172/jci97350, doi:10.1172/jci97350. This article has 58 citations and is from a highest quality peer-reviewed journal.

7. (mujtaba2015amutationof pages 4-6): Ghulam Mujtaba, Julie M Schultz, Ayesha Imtiaz, Robert J Morell, Thomas B Friedman, and Sadaf Naz. A mutation of met, encoding hepatocyte growth factor receptor, is associated with human dfnb97 hearing loss. Journal of Medical Genetics, 52:548-552, May 2015. URL: https://doi.org/10.1136/jmedgenet-2015-103023, doi:10.1136/jmedgenet-2015-103023. This article has 49 citations and is from a domain leading peer-reviewed journal.

8. (faridi2024deafnessdfnb128associated pages 8-10): Rabia Faridi, Rizwan Yousaf, Sayaka Inagaki, Rafal Olszewski, Shoujun Gu, Robert Morell, Elizabeth Wilson, Ying Xia, Tanveer Qaiser, Muhammad Rashid, Cristina Fenollar-Ferrer, Michael Hoa, Sheikh Riazuddin, and Thomas Friedman. Deafness dfnb128 associated with a recessive variant of human map3k1 recapitulates hearing loss of map3k1-deficient mice. Genes, 15:845, Jun 2024. URL: https://doi.org/10.3390/genes15070845, doi:10.3390/genes15070845. This article has 3 citations.

9. (OpenTargets Search: autosomal recessive nonsyndromic hearing loss 26): Open Targets Query (autosomal recessive nonsyndromic hearing loss 26, 37 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

10. (faridi2024deafnessdfnb128associated pages 1-2): Rabia Faridi, Rizwan Yousaf, Sayaka Inagaki, Rafal Olszewski, Shoujun Gu, Robert Morell, Elizabeth Wilson, Ying Xia, Tanveer Qaiser, Muhammad Rashid, Cristina Fenollar-Ferrer, Michael Hoa, Sheikh Riazuddin, and Thomas Friedman. Deafness dfnb128 associated with a recessive variant of human map3k1 recapitulates hearing loss of map3k1-deficient mice. Genes, 15:845, Jun 2024. URL: https://doi.org/10.3390/genes15070845, doi:10.3390/genes15070845. This article has 3 citations.

11. (naz2020growthfactorand pages 5-7): Sadaf Naz and Thomas B. Friedman. Growth factor and receptor malfunctions associated with human genetic deafness. Clinical Genetics, 97:138-155, Oct 2020. URL: https://doi.org/10.1111/cge.13641, doi:10.1111/cge.13641. This article has 17 citations and is from a peer-reviewed journal.

12. (mujtaba2015amutationof pages 6-8): Ghulam Mujtaba, Julie M Schultz, Ayesha Imtiaz, Robert J Morell, Thomas B Friedman, and Sadaf Naz. A mutation of met, encoding hepatocyte growth factor receptor, is associated with human dfnb97 hearing loss. Journal of Medical Genetics, 52:548-552, May 2015. URL: https://doi.org/10.1136/jmedgenet-2015-103023, doi:10.1136/jmedgenet-2015-103023. This article has 49 citations and is from a domain leading peer-reviewed journal.

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All extracted references resolved successfully.

Term Validation

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

Every term resolved, and every label the report gave matched.