Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...

Cardiomyopathy II: Dilated Cardiomyopathy

Cardiomyopathy II: Dilated Cardiomyopathy

Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...

Cardiomyopathy IV: Restrictive Cardiomyopathy

Cardiomyopathy IV: Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...

Comparing Copy Number Variations and SNPs

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...

Alternative RNA Splicing

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Cardiologists' perspectives on sociocultural and structural factors shaping cardiovascular genetic testing.

medRxiv : the preprint server for health sciences·2026

Same author

A pilot qualitative study of patient understanding and perceptions of genetic counselors and cascade testing in the context of transthyretin cardiac amyloidosis.

Journal of genetic counseling·2026

Same author

Effects of 100% oxygen during deferred cord clamping on oxidative stress markers: a sub-study of a randomized controlled trial.

Pediatric research·2026

Same author

The IMPACT-FH Renewal Protocol: Evaluating FH Cascade Testing Implementation in Primary Care through a Pragmatic Trial, Economic Evaluation, and Mixed-Methods Sustainability Assessment.

Public health genomics·2026

Same author

Endovascular treatment for medium or distal vessel occlusion stroke (DISTAL): 12-month outcomes of a multicentre, open-label, randomised trial.

The Lancet. Neurology·2026

Same author

Functional evaluation of TRPC6 missense variants in cancer patients via molecular docking analysis compared with patch Clamp electrophysiology.

The Journal of biological chemistry·2026

Search research articles

Related Experiment Video

Updated: Jun 5, 2026

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

SCN5A rare variants in familial dilated cardiomyopathy decrease peak sodium current depending on the common

Jianding Cheng¹, Ana Morales, Jill D Siegfried

¹Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA.

Clinical and Translational Science

|December 21, 2010

Summary

Two novel SCN5A variants, R222Q and I1835T, are linked to dilated cardiomyopathy (DCM). Their impact on sodium current (I(Na)) depends on common SCN5A variants, suggesting a role in DCM causation.

More Related Videos

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes

Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes

Published on: March 12, 2013

Related Experiment Videos

Last Updated: Jun 5, 2026

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes

Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes

Published on: March 12, 2013

Area of Science:

Genetics
Cardiology
Molecular Biology

Background:

Dilated cardiomyopathy (DCM) is a complex heart condition.
Identifying genetic causes of DCM is crucial for diagnosis and treatment.
The SCN5A gene plays a vital role in cardiac sodium channel function.

Purpose of the Study:

To investigate the functional impact of two novel SCN5A rare variants (R222Q and I1835T) on sodium current (I(Na)).
To determine if the effects of these variants are modulated by common SCN5A polymorphisms, specifically H558R.
To provide evidence for the relevance of these SCN5A variants in DCM causation.

Main Methods:

Constructed cDNAs with rare SCN5A variants (R222Q, I1835T) in different common variant backgrounds (Q1077del, Q1077).
Expressed variants in HEK293 cells and studied sodium current (I(Na)) using whole-cell voltage clamp.
Analyzed I(Na) density, inactivation, activation, and recovery from inactivation.

Main Results:

In the Q1077del background, combined variants R222Q/H558R and I1835T/H558R significantly reduced I(Na) density and slowed recovery from inactivation.
R222Q and R222Q/H558R showed negative shifts in activation and inactivation; I1835T/H558R showed a negative shift in inactivation.
No significant changes in I(Na) were observed in the Q1077 background, indicating dependence on the common variant background.

Conclusions:

The biophysical effects of novel SCN5A variants R222Q and I1835T are dependent on the common SCN5A H558R polymorphism.
These findings provide functional evidence supporting the role of these novel SCN5A variants in dilated cardiomyopathy.
Understanding variant interactions is key to deciphering the genetic basis of DCM.