| Domain | Disease-specific finding | Evidence type | Key quantitative detail | Source/year |
|---|---|---|---|---|
| Identity | Dilated cardiomyopathy 1BB is mapped to MONDO:0013030 and linked to **DSG2** (desmoglein-2); evidence base is small and overlaps strongly with broader DSG2-associated arrhythmogenic cardiomyopathy literature | Curated disease-target association | 1 disease-target association listed for DCM1BB: DSG2 | Open Targets disease-target mapping (pqac-00000000) |
| Human genetics: p.Arg119Ter | Heterozygous **DSG2 p.Arg119Ter** occurs in cardiomyopathy patients with variable phenotypes including DCM; supports desmosomal impairment as a contributor/exacerbator rather than proving fully penetrant monogenic DCM1BB alone | Human cohort/case series | 4 unrelated carriers among 808 nonischemic cardiomyopathy patients; cohort allele frequency **0.0037**; described as **>50-fold** above general Japanese population; diagnoses included ARVC, DCM after VSD repair, DCM, end-stage HCM | Sumida et al., 2024 (pqac-00000016) |
| Human genetics: p.Phe531Cys family | Homozygous **DSG2 p.Phe531Cys / F531C** segregated with severe familial ACM featuring fibrosis/dysfunction; highly informative for DSG2 biology, but broader ACM evidence rather than direct DCM1BB nomenclature | Human family study + knock-in model | **8 affected family members**, all homozygous; desmosomal-gene variants account for **~two-thirds** of ACM; DSG2 described as second most prevalent ACM gene | Zhang et al., 2024 (pqac-00000013) |
| Human cellular disease model | Complete DSG2 deficiency can present clinically as severe juvenile-onset biventricular cardiomyopathy diagnosed as idiopathic DCM, supporting DSG2-deficient DCM as a real disease mechanism | Human case + iPSC-derived cardiomyocytes | Homozygous **c.355C>T (p.R119X)**; VAD implantation at **age 21**; heterozygous parents unaffected; mutant tissue-ring force reduced and corrected after repair | Shiba et al., 2021 (pqac-00000004, pqac-00000006) |
| iPSC correction / AAV rescue | Disease phenotypes from DSG2 deficiency were reversed by isogenic correction and improved by AAV-mediated DSG2 replacement, providing preclinical precision-medicine proof of concept | Human iPSC-CM and engineered tissue | Contractile force improved from **49 ± 6 to 86 ± 1 μN** after correction; AAV-mediated DSG2 replacement significantly recovered contraction force | Shiba et al., 2021 (pqac-00000003, pqac-00000006) |
| 2024 immune mechanism | In DSG2-mutant mouse ACM, **NFκB signaling in cardiomyocytes** recruits **CCR2+ macrophages**, driving myocardial injury, dysfunction, arrhythmias, and fibro-inflammatory remodeling; mechanistically relevant but preclinical and broader ACM | Mouse genetics + single-nucleus/single-cell profiling | Disease prevented/attenuated when cardiac-myocyte NFκB signaling was blocked; snRNA-seq/CITE-seq implicated cardiomyocytes, fibroblasts, and CCR2+ macrophages | Chelko et al., 2024 (pqac-00000015) |
| 2024 fibrosis mechanism | Variant DSG2 protein can misfold in the ER, activate **BiP → PERK → ATF4 → TGF-β1**, and stimulate fibroblasts paracrinally, explaining progressive fibrosis in DSG2 cardiomyopathy | Human family-supported mouse/mechanistic study | Inhibition of PERK-ATF4 attenuated fibrosis and systolic dysfunction in **Dsg2F536C/F536C** mice | Zhang et al., 2024 (pqac-00000013) |
| 2024 exercise interaction | Endurance training can unmask a right-ventricular arrhythmogenic phenotype in **heterozygous Dsg2** mice; relevant gene-environment interaction for DSG2 disease counseling | Mouse exercise model | DSG2 mutations reported in **5–10%** of ARVC; training increased RV diameter, decreased RV function, prolonged activation times, and induced pacing-triggered arrhythmia without obvious fibrosis/inflammation | Fabritz et al., 2024 (pqac-00000016) |
| Diagnostic implementation | Current care relies on phenotype-first cardiomyopathy workup with **echocardiography, CMR, ECG/Holter, biomarkers, pedigree analysis, and genetic testing/counseling**; DCM1BB has no standalone diagnostic criteria beyond inherited cardiomyopathy practice | Guideline/review | Genetic testing is described as a **first-tier diagnostic test for every patient with DCM**; CMR is gold standard for fibrosis/phenotyping; imaging + genetics guide ICD decisions | Stroeks et al., 2023; Grasso et al., 2024; Gasior, 2024 (pqac-00000011, pqac-00000009, pqac-00000012) |
| Epidemiology caveat | There are **no subtype-specific prevalence/incidence data** for DCM1BB; only broader DCM/ACM estimates are available, so population burden must be inferred cautiously | Review / broader disease epidemiology | ACM prevalence estimated **1:2000–1:5000**; DCM prevalence estimated **~1:220 to 1:250** in modern datasets, far higher than older **~1:2500** estimates | Vencato et al., 2024; Newman & Burke, 2024 (pqac-00000014, pqac-00000010) |
| Therapy status | **No DSG2-specific approved therapy** and **no DSG2-specific registered interventional clinical trial** were identified; current treatment remains standard HF/arrhythmia management, while gene therapy evidence is preclinical | Clinical-trial search + literature | Identified ACM trials were observational or targeted other genes/inflammatory pathways (e.g., PKP2 gene therapy), not DSG2-specific | Clinical-trial search context + field literature (pqac-00000000) |


*Table: This table summarizes the most decision-relevant evidence for DSG2-associated dilated cardiomyopathy 1BB, distinguishing direct DCM1BB findings from broader DSG2-arrhythmogenic cardiomyopathy data. It is useful for rapidly identifying what is established in humans, what remains preclinical, and where evidence gaps persist.*