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Cardiogenetics
Volume 8
Issue 1
10.4081/cardiogenetics.2018.7127
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Article

Lamin-A/C Variants Found in Patients with Cardiac Conduction Disease Reduce Sodium Currents

by
Michael A. Olaopa
1,
Katherine G. Spoonamore
1,
Deepak Bhakta
1,
Zhenhui Chen
1,
Patricia B.S. Celestino-Soper
2,
Peng-Sheng Chen
1,
Tomohiko Ai
1,3,* and
Matteo Vatta
1,2,*
1
Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
2
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
3
Division of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
*
Authors to whom correspondence should be addressed.
Cardiogenetics 2018, 8(1), 7127; https://doi.org/10.4081/cardiogenetics.2018.7127
Submission received: 7 October 2017 / Revised: 7 October 2017 / Accepted: 12 December 2017 / Published: 22 February 2018

Abstract

Variants in the LMNA gene, which encodes Lamin-A/C, have been commonly associated with cardiac conduction system diseases usually accompanying cardiomyopathy. We have seen two unrelated patients who presented with atrioventricular block (AVB) with or without cardiomyopathy. Genetic testing identified the LMNA missense variant c.1634G>A (p.R545H) and the single nucleotide deletion c.859delG (p.A287Lfs*193). The deletion leads to a shift in the reading frame and subsequent protein truncation. Since impaired Nav1.5 function has been reported to cause AVB, we sought to investigate the effects of abnormal Lamins on Nav1.5 in HEK-293 cells using patch-clamp methods. Patch-clamp studies showed that p.R545H decreased the peak INa by approximately 70%. The voltage-dependency of steady state inactivation was rightward shifted in the cells transfected with p.R545H. The p.A287Lfs*193 also decreased the peak INa by approximately 62%. The voltagedependency of steady state inactivation was rightward shifted in the cells transfected with p.A287Lfs*193. Variants of the LMNA gene caused significant reduction of the peak INa in HEK-293 cells, which may account for the patients’ AVB.
Keywords: Lamin A/C; atrioventricular block; cardiomyopathy; sodium channel Lamin A/C; atrioventricular block; cardiomyopathy; sodium channel

Share and Cite

MDPI and ACS Style

Olaopa, M.A.; Spoonamore, K.G.; Bhakta, D.; Chen, Z.; Celestino-Soper, P.B.S.; Chen, P.-S.; Ai, T.; Vatta, M. Lamin-A/C Variants Found in Patients with Cardiac Conduction Disease Reduce Sodium Currents. Cardiogenetics 2018, 8, 7127. https://doi.org/10.4081/cardiogenetics.2018.7127

AMA Style

Olaopa MA, Spoonamore KG, Bhakta D, Chen Z, Celestino-Soper PBS, Chen P-S, Ai T, Vatta M. Lamin-A/C Variants Found in Patients with Cardiac Conduction Disease Reduce Sodium Currents. Cardiogenetics. 2018; 8(1):7127. https://doi.org/10.4081/cardiogenetics.2018.7127

Chicago/Turabian Style

Olaopa, Michael A., Katherine G. Spoonamore, Deepak Bhakta, Zhenhui Chen, Patricia B.S. Celestino-Soper, Peng-Sheng Chen, Tomohiko Ai, and Matteo Vatta. 2018. "Lamin-A/C Variants Found in Patients with Cardiac Conduction Disease Reduce Sodium Currents" Cardiogenetics 8, no. 1: 7127. https://doi.org/10.4081/cardiogenetics.2018.7127

APA Style

Olaopa, M. A., Spoonamore, K. G., Bhakta, D., Chen, Z., Celestino-Soper, P. B. S., Chen, P. -S., Ai, T., & Vatta, M. (2018). Lamin-A/C Variants Found in Patients with Cardiac Conduction Disease Reduce Sodium Currents. Cardiogenetics, 8(1), 7127. https://doi.org/10.4081/cardiogenetics.2018.7127

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