Related Experiment Video
Updated: Jul 16, 2026
Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes
Published on: March 12, 2013
N- and C-terminal KCNE1 mutations cause distinct phenotypes of long QT syndrome
Seiko Ohno1, Dimitar P Zankov, Hidetada Yoshida
1Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Background:
Long QT syndromes (LQTS) are inherited diseases involving mutations to genes encoding a number of cardiac ion channels and a membrane adaptor protein. The MinK protein is a cardiac K-channel accessory subunit encoded by the KCNE1 gene, mutations of which are associated with the LQT5 form of LQTS.
Objective:
The purpose of this study was to search for the KCNE1 mutations and clarify the function of those mutations.
Methods:
We conducted a genetic screen of KCNE1 mutations in 151 Japanese LQTS patients using the denaturing high-performance liquid chromatography-WAVE system and direct sequencing. In two LQTS patients, we identified two KCNE1 missense mutations, located in the MinK N- and C-terminal domains. The functional effects of these mutations were examined by heterologous coexpression with KCNQ1 and KCNH2.
Results:
One mutation, which was identified in a 67-year-old woman, A8V, was novel. Her electrocardiogram (ECG) revealed marked bradycardia and QT interval prolongation. Another mutation, R98W, was identified in a 19-year-old woman. She experienced syncope followed by palpitation in exercise. At rest, her ECG showed bradycardia with mild QT prolongation, which became more prominent during exercise. In electrophysiological analyses, R98W produced reduced I(Ks) currents with a positive shift in the half activation voltages. In addition, when the A8V mutation was coexpressed with KCNH2, this reduced current magnitude, which is suggestive of a modifier effect by the A8V KCNE1 mutation on I(Kr).
Conclusion:
KCNE1 mutations may be associated with mild LQTS phenotypes, and KCNE1 gene screening is of clinical importance for asymptomatic and mild LQTS patients.
Insights
Genetic screening identified two KCNE1 mutations in Japanese Long QT syndrome (LQTS) patients. These mutations, A8V and R98W, impact cardiac ion channel function, potentially causing mild LQTS phenotypes.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Ion Channel Physiology
Background:
- Long QT syndromes (LQTS) are inherited cardiac arrhythmias linked to ion channel gene mutations.
- KCNE1 gene encodes the MinK protein, a cardiac K-channel accessory subunit.
- Mutations in KCNE1 are associated with LQT5, a specific form of LQTS.
Observation:
- A genetic screen of 151 Japanese LQTS patients identified two KCNE1 missense mutations (A8V and R98W).
- The A8V mutation was novel, found in a patient with marked bradycardia and QT prolongation.
- The R98W mutation was identified in a patient experiencing syncope and palpitations, with exercise-induced QT prolongation.
Findings:
- Electrophysiological analysis revealed that the R98W mutation reduced I(Ks) currents and shifted activation voltages.
- Coexpression of A8V with KCNH2 reduced I(Kr) current magnitude, suggesting a modifier effect.
- These KCNE1 mutations were associated with varying degrees of QT interval prolongation and cardiac symptoms.
Implications:
- KCNE1 mutations may contribute to mild or asymptomatic Long QT syndrome phenotypes.
- Genetic screening of the KCNE1 gene is clinically important for identifying at-risk individuals, including those with mild or no symptoms.
- Understanding KCNE1 mutation function aids in diagnosing and managing LQTS patients.
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
01:39Mutations