DSC2 (Desmocollin-2)
Details
DSC2 encodes desmocollin-2, one of two cardiac-predominant desmosomal cadherins (together with desmoglein-2/DSG2) mediating cell-cell adhesion at the intercalated disc. LP/P variants in DSC2 cause a form of ARVC phenotypically similar to PKP2-associated classical ARVC. DSC2 accounts for a small percentage of ACM cases, and autosomal recessive inheritance is often observed.
Key Facts
- Inheritance: Autosomal dominant, but autosomal recessive forms are common (homozygous DSC2 mutations associated with ARVC). (sources/ACM-Genotype-Mx-JCE-2024, rating: high)
- Phenotype: Classical 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)
- Penetrance: Insufficient data available to describe penetrance in detail. Small case reports dominate the literature. (sources/ACM-Genotype-Mx-JCE-2024)
- DSC2 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 essentially absent — most information is from small case reports/series.
- The relative contributions of autosomal dominant vs recessive inheritance patterns need clarification.
- As with DSG2, whether DSC2-specific management adjustments are warranted is unknown.
Connections
- Related to entities/DSG2
- 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