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

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

JACC: Basic to Translational Science (Feb 2017)

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

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

Affiliations

Ann P. Quick, BA: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas
Andrew P. Landstrom, MD, PhD: Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas; Department of Pediatrics (Cardiology), Baylor College of Medicine, Houston, Texas
Qiongling Wang, PhD: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas
David L. Beavers, MD, PhD: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas
Julia O. Reynolds, BS: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas
Giselle Barreto-Torres, PhD: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas
Viet Tran, MD: Department of Medicine (Cardiology), Baylor College of Medicine, Houston, Texas
Jordan Showell, BS: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas
Leonne E. Philippen, MSc: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas
Shaine A. Morris MD, MPH: Department of Pediatrics (Cardiology), Baylor College of Medicine, Houston, Texas
Darlene Skapura, BS: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas
J. Martijn Bos, MD: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota
Steen E. Pedersen, PhD: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas
Robia G. Pautler, PhD: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas
Michael J. Ackerman, MD, PhD: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota
Xander H.T. Wehrens, MD, PhD: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas; Department of Medicine (Cardiology), Baylor College of Medicine, Houston, Texas; Address for correspondence: Dr. Xander H.T. Wehrens, Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, BCM335, Houston, Texas 77030.

Journal volume & issue: Vol. 2, no. 1
pp. 56 – 67

Abstract

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Summary: 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-405âlocated within the alpha helix domainâwith 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. Key Words: calcium, hypertrophic cardiomyopathy, junctophilin-2, magnetic resonance imaging

Published in JACC: Basic to Translational Science

ISSN: 2452-302X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.journals.elsevier.com/jacc-basic-to-translational-science/

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