Genotype-phenotype correlation of 139 p.Gln530Ter-KCNQ1 patients with inherited long QT syndrome
Savelev, Aleksei A LU
; Larsson, Nina
LU
; Dahlberg, Pia
LU
; Christensen, Alex H
; Bugge, Cecilie
; Bulatovic, Ivana
; Gardovic, Teodora
; Svensson, Anneli
LU
; Ljungström, Erik
and Markljung, Minna
, et al.
(2026)
In Heart Rhythm
23(7).
p.1149-1155
- Abstract
BACKGROUND: Variants in the KCNQ1 underlie type 1 long QT syndrome. The clinical manifestations are influenced by the specific KCNQ1 pathogenic variant.
OBJECTIVE: We aimed to describe the phenotype in patients found to possess the p.Gln530Ter-KCNQ1 pathogenic variant common in Scandinavian patients with long QT syndrome.
METHODS: Clinical characteristics of p.Gln530Ter-KCNQ1 variant-positive patients from 6 university hospital registries in Sweden, Denmark, Norway, and the United States were compared with carriers of other KCNQ1 pathogenic variants (non-p.Gln530Ter-KCNQ1) and gene-negative controls. Cardiac events (CEs) encompassed syncope of unknown origin and ventricular arrhythmias (VAs) (episodes of torsades de pointes,... (More)
BACKGROUND: Variants in the KCNQ1 underlie type 1 long QT syndrome. The clinical manifestations are influenced by the specific KCNQ1 pathogenic variant.
OBJECTIVE: We aimed to describe the phenotype in patients found to possess the p.Gln530Ter-KCNQ1 pathogenic variant common in Scandinavian patients with long QT syndrome.
METHODS: Clinical characteristics of p.Gln530Ter-KCNQ1 variant-positive patients from 6 university hospital registries in Sweden, Denmark, Norway, and the United States were compared with carriers of other KCNQ1 pathogenic variants (non-p.Gln530Ter-KCNQ1) and gene-negative controls. Cardiac events (CEs) encompassed syncope of unknown origin and ventricular arrhythmias (VAs) (episodes of torsades de pointes, appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, or sudden cardiac death).
RESULTS: The p.Gln530Ter-KCNQ1, non-p.Gln530Ter-KCNQ1, and control groups included 139 (65% female; 24% probands; mean age at end of follow-up 51 ± 20 years), 194 (65% female; mean age 44 ± 19), and 717 individuals (55% female; mean age 39 ± 24), respectively. CEs by 60 years of age were reported in 30 of the p.Gln530Ter-KCNQ1 group (22%; of those 5 VA, all nonfatal), 46 of the non-p.Gln530Ter-KCNQ1 group (24%; 4 VA, all nonfatal), and 81 of controls (11%; no VA). In the p.Gln530Ter-KCNQ1 group, CE occurred at a significantly older age than in the non-p.Gln530Ter-KCNQ1 group (44 ± 22 vs 31 ± 22; P = .02). Before 30 years of age, CE risk in the p.Gln530Ter-KCNQ1 group did not differ from that in controls (adjusted hazard ratio 1.11 [95% confidence interval 0.65-1.89]; P = .707) and was significantly lower than in the non-p.Gln530Ter-KCNQ1 group. After 30 years of age, CE risk in the p.Gln530Ter-KCNQ1 group increased significantly (adjusted hazard ratio 3.21 [95% confidence interval 1.49-6.92]; P = .003, compared with controls) and did not differ from the non-p.Gln530Ter-KCNQ1 group.
CONCLUSION: The p.Gln530Ter-KCNQ1 variant is associated with a later onset of CE than other KCNQ1 pathogenic variants.
(Less)
- author
- Savelev, Aleksei A
LU
; Larsson, Nina
LU
; Dahlberg, Pia
LU
; Christensen, Alex H
; Bugge, Cecilie
; Bulatovic, Ivana
; Gardovic, Teodora
; Svensson, Anneli
LU
; Ljungström, Erik
and Markljung, Minna
, et al. (More)
- Savelev, Aleksei A
LU
; Larsson, Nina
LU
; Dahlberg, Pia
LU
; Christensen, Alex H
; Bugge, Cecilie
; Bulatovic, Ivana
; Gardovic, Teodora
; Svensson, Anneli
LU
; Ljungström, Erik
; Markljung, Minna
; Ringborn, Michael
; Lundin, Catarina
LU
; Goldenberg, Ilan
; McNitt, Scott
; Polonsky, Bronislava
; Graff, Claus
; Zareba, Wojciech
; Haugaa, Kristina H
and Platonov, Pyotr G
LU
(Less)
- organization
- publishing date
- 2026-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adult, Female, Humans, Male, Middle Aged, DNA/genetics, Electrocardiography, Follow-Up Studies, Genetic Association Studies, Genotype, KCNQ1 Potassium Channel/genetics, Long QT Syndrome/genetics, Mutation, Phenotype, Romano-Ward Syndrome/genetics
- in
- Heart Rhythm
- volume
- 23
- issue
- 7
- pages
- 1149 - 1155
- publisher
- Elsevier
- external identifiers
-
- pmid:41881367
- scopus:105044540324
- ISSN
- 1547-5271
- DOI
- 10.1016/j.hrthm.2026.03.1911
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2026 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
- id
- e5ba44f6-edec-4da6-95cf-785dc5290f40
- date added to LUP
- 2026-08-24 08:56:56
- date last changed
- 2026-08-25 04:02:24
@article{e5ba44f6-edec-4da6-95cf-785dc5290f40,
abstract = {{<p>BACKGROUND: Variants in the KCNQ1 underlie type 1 long QT syndrome. The clinical manifestations are influenced by the specific KCNQ1 pathogenic variant.</p><p>OBJECTIVE: We aimed to describe the phenotype in patients found to possess the p.Gln530Ter-KCNQ1 pathogenic variant common in Scandinavian patients with long QT syndrome.</p><p>METHODS: Clinical characteristics of p.Gln530Ter-KCNQ1 variant-positive patients from 6 university hospital registries in Sweden, Denmark, Norway, and the United States were compared with carriers of other KCNQ1 pathogenic variants (non-p.Gln530Ter-KCNQ1) and gene-negative controls. Cardiac events (CEs) encompassed syncope of unknown origin and ventricular arrhythmias (VAs) (episodes of torsades de pointes, appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, or sudden cardiac death).</p><p>RESULTS: The p.Gln530Ter-KCNQ1, non-p.Gln530Ter-KCNQ1, and control groups included 139 (65% female; 24% probands; mean age at end of follow-up 51 ± 20 years), 194 (65% female; mean age 44 ± 19), and 717 individuals (55% female; mean age 39 ± 24), respectively. CEs by 60 years of age were reported in 30 of the p.Gln530Ter-KCNQ1 group (22%; of those 5 VA, all nonfatal), 46 of the non-p.Gln530Ter-KCNQ1 group (24%; 4 VA, all nonfatal), and 81 of controls (11%; no VA). In the p.Gln530Ter-KCNQ1 group, CE occurred at a significantly older age than in the non-p.Gln530Ter-KCNQ1 group (44 ± 22 vs 31 ± 22; P = .02). Before 30 years of age, CE risk in the p.Gln530Ter-KCNQ1 group did not differ from that in controls (adjusted hazard ratio 1.11 [95% confidence interval 0.65-1.89]; P = .707) and was significantly lower than in the non-p.Gln530Ter-KCNQ1 group. After 30 years of age, CE risk in the p.Gln530Ter-KCNQ1 group increased significantly (adjusted hazard ratio 3.21 [95% confidence interval 1.49-6.92]; P = .003, compared with controls) and did not differ from the non-p.Gln530Ter-KCNQ1 group.</p><p>CONCLUSION: The p.Gln530Ter-KCNQ1 variant is associated with a later onset of CE than other KCNQ1 pathogenic variants.</p>}},
author = {{Savelev, Aleksei A and Larsson, Nina and Dahlberg, Pia and Christensen, Alex H and Bugge, Cecilie and Bulatovic, Ivana and Gardovic, Teodora and Svensson, Anneli and Ljungström, Erik and Markljung, Minna and Ringborn, Michael and Lundin, Catarina and Goldenberg, Ilan and McNitt, Scott and Polonsky, Bronislava and Graff, Claus and Zareba, Wojciech and Haugaa, Kristina H and Platonov, Pyotr G}},
issn = {{1547-5271}},
keywords = {{Adult; Female; Humans; Male; Middle Aged; DNA/genetics; Electrocardiography; Follow-Up Studies; Genetic Association Studies; Genotype; KCNQ1 Potassium Channel/genetics; Long QT Syndrome/genetics; Mutation; Phenotype; Romano-Ward Syndrome/genetics}},
language = {{eng}},
number = {{7}},
pages = {{1149--1155}},
publisher = {{Elsevier}},
series = {{Heart Rhythm}},
title = {{Genotype-phenotype correlation of 139 p.Gln530Ter-KCNQ1 patients with inherited long QT syndrome}},
url = {{http://dx.doi.org/10.1016/j.hrthm.2026.03.1911}},
doi = {{10.1016/j.hrthm.2026.03.1911}},
volume = {{23}},
year = {{2026}},
}