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

doi:10.1016/j.jacbts.2016.11.004

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

Cardiovascular Medicine

Research output: Contribution to journal › Article › peer-review

12 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 language	English (US)
Pages (from-to)	56-67
Number of pages	12
Journal	JACC: Basic to Translational Science
Volume	2
Issue number	1
DOIs	https://doi.org/10.1016/j.jacbts.2016.11.004
State	Published - 2017

Keywords

calcium
hypertrophic cardiomyopathy
junctophilin-2
magnetic resonance imaging

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jacbts.2016.11.004

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Quick, A. P., Landstrom, A. P., Wang, Q., Beavers, D. L., Reynolds, J. O., Barreto-Torres, G., Tran, V., Showell, J., Philippen, L. E., Morris, S. A., Skapura, D., Bos, J. M., Pedersen, S. E., Pautler, R. G., Ackerman, M. J., & Wehrens, X. H. T. (2017). Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic Dysfunction. JACC: Basic to Translational Science, 2(1), 56-67. https://doi.org/10.1016/j.jacbts.2016.11.004

Quick, AP, Landstrom, AP, Wang, Q, Beavers, DL, Reynolds, JO, Barreto-Torres, G, Tran, V, Showell, J, Philippen, LE, Morris, SA, Skapura, D, Bos, JM, Pedersen, SE, Pautler, RG, Ackerman, MJ & Wehrens, XHT 2017, 'Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic Dysfunction', JACC: Basic to Translational Science, vol. 2, no. 1, pp. 56-67. https://doi.org/10.1016/j.jacbts.2016.11.004

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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.",

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

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AU - Landstrom, Andrew P.

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AU - Beavers, David L.

AU - Reynolds, Julia O.

AU - Barreto-Torres, Giselle

AU - Tran, Viet

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AU - Philippen, Leonne E.

AU - Morris, Shaine A.

AU - Skapura, Darlene

AU - Bos, J. Martijn

AU - Pedersen, Steen E.

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AU - Ackerman, Michael J.

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AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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