Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic Dysfunction

Ann P. Quick, Andrew P. Landstrom, Qiongling Wang, David L. Beavers, Julia O. Reynolds, Giselle Barreto-Torres, Viet Tran, Jordan Showell, Leonne E. Philippen, Shaine A. Morris, Darlene Skapura, J. Martijn Bos, Steen E. Pedersen, Robia G. Pautler, Michael J. Ackerman, Xander H.T. Wehrens

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Junctophilin-2 (JPH2) is a structural calcium (Ca2+) handling protein, which approximates the cardiomyocyte transverse tubules (TTs) to the sarcoplasmic reticulum. This facilitates communication of the voltage-gated Ca2+ channel and the ryanodine receptor RyR2. A human patient with hypertrophic cardiomyopathy was positive for a JPH2 mutation substituting alanine-405—located within the alpha helix domain—with a serine (A405S). Using a novel mouse echocardiography plane, we found that mice bearing this JPH2 mutation developed increased subvalvular septal thickness. Cardiomyocytes from the septa of these mice displayed irregular TTs and abnormal Ca2+ handling including increased SERCA activity.

Original languageEnglish (US)
Pages (from-to)56-67
Number of pages12
JournalJACC: Basic to Translational Science
Volume2
Issue number1
DOIs
StatePublished - 2017

Keywords

  • calcium
  • hypertrophic cardiomyopathy
  • junctophilin-2
  • magnetic resonance imaging

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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