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 John Ackerman, Xander H.T. Wehrens

Research output: Contribution to journalArticle

8 Citations (Scopus)

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

Fingerprint

Hypertrophy
Ryanodine Receptor Calcium Release Channel
Cardiac Myocytes
Mutation
Hypertrophic Cardiomyopathy
Sarcoplasmic Reticulum
Alanine
Serine
Echocardiography
Communication
Calcium
junctophilin
Proteins
alpha-Helical Protein Conformation
Handling (Psychology)

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Quick, A. P., Landstrom, A. P., Wang, Q., Beavers, D. L., Reynolds, J. O., Barreto-Torres, G., ... 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

Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic Dysfunction. / Quick, Ann P.; Landstrom, Andrew P.; Wang, Qiongling; Beavers, David L.; Reynolds, Julia O.; Barreto-Torres, Giselle; Tran, Viet; Showell, Jordan; Philippen, Leonne E.; Morris, Shaine A.; Skapura, Darlene; Bos, J. Martijn; Pedersen, Steen E.; Pautler, Robia G.; Ackerman, Michael John; Wehrens, Xander H.T.

In: JACC: Basic to Translational Science, Vol. 2, No. 1, 2017, p. 56-67.

Research output: Contribution to journalArticle

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
Quick, Ann P. ; Landstrom, Andrew P. ; Wang, Qiongling ; Beavers, David L. ; Reynolds, Julia O. ; Barreto-Torres, Giselle ; Tran, Viet ; Showell, Jordan ; Philippen, Leonne E. ; Morris, Shaine A. ; Skapura, Darlene ; Bos, J. Martijn ; Pedersen, Steen E. ; Pautler, Robia G. ; Ackerman, Michael John ; Wehrens, Xander H.T. / Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic Dysfunction. In: JACC: Basic to Translational Science. 2017 ; Vol. 2, No. 1. pp. 56-67.
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