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Cardiogenetics, Volume 13, Issue 3

2023 September - 3 articles

Cover Story: The hyperpolarization-activated ‘funny current’ (I_f) is a key player in the pacemaker activity of the sinus node. It flows through ion channels encoded by the HCN4 gene and contributes to the spontaneous diastolic depolarization of the sinus node cells. Patients carrying the heterozygous A414G mutation in HCN4 typically present with moderate-to-severe sinus bradycardia. Our in vitro patch clamp experiments demonstrate that the A414G mutation affects the voltage dependence of the I_f channels in such a way that less channels are active in the voltage range of diastolic depolarization. Our subsequent in silico experiments, based on our data acquired in vitro, show that diastolic depolarization is significantly slowed down by the A414G mutation, in particular under vagal tone and in the presence of atrial load, explaining the clinically observed sinus bradycardia. View this paper

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Article

1 Citations

4,459 Views

18 Pages

Functional Characterization of the A414G Loss-of-Function Mutation in HCN4 Associated with Sinus Bradycardia

Arie O. Verkerk and
Ronald Wilders

Cardiogenetics2023, 13(3), 117-134;https://doi.org/10.3390/cardiogenetics13030012

4 August 2023

Patients carrying the heterozygous A414G mutation in the HCN4 gene, which encodes the HCN4 protein, demonstrate moderate to severe bradycardia of the heart. Tetramers of HCN4 subunits compose the ion channels in the sinus node that carry the hyperpol...

(This article belongs to the Section Molecular & Translational Genetics)

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Editorial

2,979 Views

4 Pages

Unraveling the Genetic and Epigenetic Complexities of Hereditary Aortic Diseases and the Breakthroughs of Precision Medicine: An Editorial

Fares Awa,
Mays Tawayha and
Wassim Mosleh

Cardiogenetics2023, 13(3), 113-116;https://doi.org/10.3390/cardiogenetics13030011

18 July 2023

The field of genetics in cardiovascular disease has introduced new possibilities for understanding the fundamental causes of aortic diseases [...]

(This article belongs to the Section Cardiovascular Genetics in Clinical Practice)

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Case Report

3 Citations

4,604 Views

7 Pages

GMDS Intragenic Deletions Associate with Congenital Heart Disease including Ebstein Anomaly

Shirley M. Lo-A-Njoe,
Eline A. Verberne,
Lars T. van der Veken,
Eric Arends,
J. Peter van Tintelen,
Alex V. Postma and
Mieke M. van Haelst

Cardiogenetics2023, 13(3), 106-112;https://doi.org/10.3390/cardiogenetics13030010

6 July 2023

Ebstein anomaly is a rare heterogeneous congenital heart defect (CHD) with a largely unknown etiology. We present a 6-year-old girl with Ebstein anomaly, atrial septum defect, hypoplastic right ventricle, and persistent left superior vena cava who ha...

(This article belongs to the Section Rare Cardiovascular Disorders)

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Cardiogenetics - ISSN 2035-8148

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