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

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 hypertro...

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Main Authors:	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
Format:	Article
Language:	English
Published:	Elsevier 2017-02-01
Series:	JACC: Basic to Translational Science
Online Access:	http://www.sciencedirect.com/science/article/pii/S2452302X1630170X

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spelling	doaj-d086c9c35bcd4a099db4e3951cde466e2020-11-24T20:59:23ZengElsevierJACC: Basic to Translational Science2452-302X2017-02-01215667Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic DysfunctionAnn P. Quick, BA0Andrew P. Landstrom, MD, PhD1Qiongling Wang, PhD2David L. Beavers, MD, PhD3Julia O. Reynolds, BS4Giselle Barreto-Torres, PhD5Viet Tran, MD6Jordan Showell, BS7Leonne E. Philippen, MSc8Shaine A. Morris MD, MPH9Darlene Skapura, BS10J. Martijn Bos, MD11Steen E. Pedersen, PhD12Robia G. Pautler, PhD13Michael J. Ackerman, MD, PhD14Xander H.T. Wehrens, MD, PhD15Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TexasCardiovascular Research Institute, Baylor College of Medicine, Houston, Texas; Department of Pediatrics (Cardiology), Baylor College of Medicine, Houston, TexasDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TexasDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TexasDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TexasDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TexasDepartment of Medicine (Cardiology), Baylor College of Medicine, Houston, TexasDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TexasDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TexasDepartment of Pediatrics (Cardiology), Baylor College of Medicine, Houston, TexasDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TexasDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MinnesotaDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TexasDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TexasDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MinnesotaDepartment 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.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 imaginghttp://www.sciencedirect.com/science/article/pii/S2452302X1630170X
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	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
spellingShingle	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 Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic Dysfunction JACC: Basic to Translational Science
author_facet	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
author_sort	Ann P. Quick, BA
title	Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic Dysfunction
title_short	Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic Dysfunction
title_full	Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic Dysfunction
title_fullStr	Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic Dysfunction
title_full_unstemmed	Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic Dysfunction
title_sort	novel junctophilin-2 mutation a405s is associated with basal septal hypertrophy and diastolic dysfunction
publisher	Elsevier
series	JACC: Basic to Translational Science
issn	2452-302X
publishDate	2017-02-01
description	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
url	http://www.sciencedirect.com/science/article/pii/S2452302X1630170X
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Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic Dysfunction

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