| Evidence/source and date | Cohort/model | Variant/intervention | Phenotype or quantitative outcome | Interpretation/evidence type |
|---|---|---|---|---|
| Schrauwen et al., *Am J Hum Genet* (2012-10-05) | 3 consanguineous Iranian families (Sh10, Sh11, He) | **CABP2 c.637+1G>T**, predicted exon 6 skipping; **p.Phe164Serfs*4** | Moderate-to-severe **sensorineural** hearing impairment; founder effect supported by shared **0.52 Mb haplotype**; variant absent in **100 Iranian controls**; truncated protein showed altered Ca²⁺ binding and less potent **CaV1.3** regulation (pqac-00000017, pqac-00000003, pqac-00000007) | Primary human genetics + functional in vitro evidence establishing DFNB93 mechanism via hypofunctional CaBP2 |
| Picher et al., *PNAS* (2017-02) | 2 affected siblings from Northern Italy + family segregation | **CABP2 c.466G>T (p.Glu156Ter / p.E156X)** | Prelingual, bilateral, symmetric **moderate-to-severe** hearing impairment with characteristic **U-shaped/mid-frequency** emphasis affecting communication; no syndromic features on clinical exam; variant absent in **225 white controls** and not reported in ExAC in cited study context (pqac-00000016, pqac-00000002) | Primary human clinical-genetic evidence for an independent CABP2 loss-of-function DFNB93 family |
| Koohiyan et al., *Audiol Neurotol* (2019-10) | Consanguineous Iranian family; 2 affected relatives/siblings in multigenerational pedigree | **CABP2 c.311G>A (p.Gly104Asp)** | **Prelingual bilateral severe** sensorineural hearing loss; segregated homozygously in affected relatives; absent in **50 normal-hearing controls** from same population; study states zero frequency in **1000 Genomes** and **ExAC** (pqac-00000005, pqac-00000006, pqac-00000021, pqac-00000023) | Primary human genetics showing phenotypic heterogeneity, extending CABP2 from moderate/severe to severe DFNB93 |
| Nawaz et al., *Heliyon* (available online 2023-12-14; 2024 issue) | Egyptian family A; 2 affected siblings with DASS background due to separate **LTBP3** defect | **CABP2 c.590T>C (p.Ile197Thr)** | Hearing impairment in Egyptian siblings was reported as having a **separate transmission mechanism independent of LTBP3**; both siblings homozygous for CABP2 missense variant while mother heterozygous (pqac-00000018) | Recent blended-phenotype report; supports CABP2 as contributor to hearing loss but not isolated DFNB93-only family ascertainment |
| Picher et al., *PNAS* (2017-02) | **Cabp2** knockout mouse (**Cabp2LacZ/LacZ**) | Genetic disruption of **Cabp2** | Elevated **ABR thresholds** and reduced amplitudes at **6–24 kHz**; **DPOAE** thresholds/amplitudes comparable to controls; reduced and more jittered SGN firing; preserved IHC/OHC anatomy and normal synapses with SGNs; expression stronger in **IHCs** than OHCs, also vestibular hair cells/outer retina (pqac-00000001, pqac-00000002, pqac-00000032, pqac-00000034) | Primary model-organism evidence for **auditory synaptopathy** with preserved outer hair cell/cochlear amplification |
| Oestreicher et al., *Front Mol Neurosci* (2021-08) | Postnatal **Cabp2−/−** mice treated at **P5–P7** | **AAV2/1-Cabp2** or **AAV-PHP.eB-Cabp2** round-window gene therapy | Hearing improved in **16/24 (67%)** treated animals with **≥20 dB SPL** improvement at tested frequencies (**p<0.0001**); **ABR wave I** amplitude increased from **0.8±0.1 µV** to **1.3±0.2 µV** at 80 dB SPL (**p<0.001**); PHP.eB achieved about **98% IHC transduction**; DPOAEs largely unaffected in mutants (pqac-00000008, pqac-00000009, pqac-00000010, pqac-00000011) | Preclinical translational proof-of-concept that CABP2 deficiency is at least partially reversible by inner-ear gene augmentation |
| Oestreicher et al., *eLife* Version of Record (2024-12-24) | **Cabp1/2 double-knockout** mice | Loss of **CaBP1 + CaBP2**; rescue by transgenic/AAV-mediated CaBP2 re-expression | Severe auditory dysfunction: click **ABR threshold 59±2 dB SPL vs 30±2 WT** at 3–4 weeks (**N=8–9**), worsening to **68±5 dB SPL vs 30±1 WT** by 7–13 weeks (**N=7**); preserved ribbon density **12.9±0.2 WT vs 12.8±0.8 DKO synapses/cell**; SGN adaptation ratio **12.5±3.0 vs 3.4±0.2 WT, p<0.00001**; sound-responsive neuron yield **0.3/h vs 2.5/h WT**; rescue substantially recovered IHC synaptic function, **ABR wave I** amplitudes, and thresholds (pqac-00000015, pqac-00000029, pqac-00000030, pqac-00000031) | Latest mechanistic refinement: CaBP1 and CaBP2 cooperatively suppress CaV1.3 inactivation needed for sustained exocytosis and sound encoding |
| ClinicalTrials.gov **NCT06680934** (first posted 2024-11-08; recruiting) | Human registry/natural history study; **estimated n=100**; University Medical Center Goettingen | **CABP2 Patient Registry and Natural History Study** | Observational **case-only** patient registry for individuals with biallelic CABP2 variants; actual start **2024-08-16**; primary outcomes include **pure-tone audiometry** and **speech audiometry**; secondary outcomes **otoacoustic emissions** and **auditory brainstem response**; estimated completion **2049-08-16** (pqac-00000014) | Current real-world implementation creating disease-specific natural-history infrastructure for diagnostics, phenotyping, and future trial readiness |


*Table: This table summarizes the main human, model-organism, translational, and registry evidence for CABP2-related DFNB93. It highlights reported variants, core phenotypes, quantitative rescue/model findings, and the distinction between isolated DFNB93 evidence and broader/blended presentations.*