DSG2 (Desmoglein-2)
Details
DSG2 encodes desmoglein-2, one of two cardiac-predominant desmosomal cadherins (together with desmocollin-2/DSC2) that mediate cell-cell adhesion at the intercalated disc. LP/P variants in DSG2 cause a form of arrhythmogenic cardiomyopathy that is phenotypically similar to PKP2-associated classical ARVC but may have an earlier age of onset and more biventricular involvement. DSG2 accounts for a smaller percentage of ACM cases than PKP2.
Key Facts
- Inheritance: Autosomal dominant; some autosomal recessive forms with specific founder variants (e.g., homozygous DSG2 variant in East Asia causing fully penetrant ARVC with heart failure phenotype). (sources/ACM-Genotype-Mx-JCE-2024, rating: high)
- Phenotype: Classical right-dominant ARVC — precordial T-wave inversions (V1–V3), right ventricular dyskinesis due to fibro-fatty replacement. More biventricular involvement than typical PKP2-ARVC. VAs usually from RV with LBBB morphology. (sources/ACM-Genotype-Mx-JCE-2024)
- Age of onset: May be earlier than PKP2-associated ARVC. (sources/ACM-Genotype-Mx-JCE-2024)
- Penetrance: Insufficient data available to describe penetrance of LP/P DSG2 variants in detail. (sources/ACM-Genotype-Mx-JCE-2024)
- DSG2 is classified as having moderate or definite evidence for ARVC causation by the ClinGen framework (James et al., 2021). (sources/ACM-Genotype-Mx-JCE-2024)
Contradictions / Open Questions
- Penetrance data are insufficient — most knowledge is extrapolated from small case series and the overall ARVC population.
- The earlier age of onset vs PKP2 is suggested by limited data; larger genotype-stratified studies needed.
- Whether DSG2-specific risk stratification or management adjustments are warranted is unknown.
Connections
- Related to entities/DSC2
- Related to entities/PKP2
- Related to entities/DSP
- Related to entities/JUP
- Related to entities/ARVC
- Related to concepts/Arrhythmogenic-Cardiomyopathy
- Related to concepts/Desmosome
- Related to sources/ACM-Genotype-Mx-JCE-2024