One gene, two modes of inheritance, four diseases: A systematic review of the cardiac manifestation of pathogenic variants in JPH2-encoded junctophilin-2.

Journal Article (Journal Article;Review)

Rare variants in JPH2 have been associated with a range of cardiac disease, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmias, and sudden cardiac death (SCD); however, our understanding of how variants in JPH2 correspond to specific modes of inheritance and correlate clinical phenotypes has not been comprehensively explored. In this systematic review, we assess current case reports and series that describe patients with JPH2 variants and cardiac disease. We identified a total of 61 variant-positive individuals, approximately 80% of whom had some form of cardiac disease, including 47% HCM, 18% DCM, and 14% arrhythmia/SCD. In analyzing the 24 probands described in the studies, we found that autosomal recessive, loss-of-function variants are associated with severe, early onset DCM, while autosomal dominant missense variants are associated with a wider range of cardiac disease, including HCM, arrhythmia, SCD, and cardiac conduction disease.

Full Text

Duke Authors

Cited Authors

  • Parker, LE; Kramer, RJ; Kaplan, S; Landstrom, AP

Published Date

  • December 1, 2021

Published In

PubMed ID

  • 34861382

Pubmed Central ID

  • PMC9156715

Electronic International Standard Serial Number (EISSN)

  • 1873-2615

Digital Object Identifier (DOI)

  • 10.1016/j.tcm.2021.11.006


  • eng

Conference Location

  • United States