Novel Junctophilin-2 Mutation A405S Is Associated With Basal Septal Hypertrophy and Diastolic Dysfunction
oleh: 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 |
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| Diterbitkan: | Elsevier 2017-02-01 |
Deskripsi
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