What question did this study set out to answer?

The aim is to identify novel mutations in KCNQ1 and HERG associated with congenital long QT syndrome in Dutch families.

March 1, 2026

Novel KCNQ1 and HERG missense mutations in Dutch long-QT families

Key Result

Fourteen missense mutations in KCNQ1 and HERG were found in Dutch LQTS families, including eight novel mutations affecting disease diagnosis and phenotype triggers.

Key Points

The aim is to identify novel mutations in KCNQ1 and HERG associated with congenital long QT syndrome in Dutch families.
Screened 24 Dutch families for mutations in KCNQ1 and HERG.
Identified 14 missense mutations, including 8 novel.
Evaluated mutation pathogenicity through family segregation and absence in controls.
Conducted genotype-phenotype studies to assess triggers for cardiac events.
Identified 14 missense mutations, 8 of which were novel.
Three novel mutations in KCNQ1: Y184S, S373P, W392R.
Five novel mutations in HERG: A558P, R582C, G604S, T613M, F640L.
Asymptomatic carriers identified, but still at risk for arrhythmias.

Structured PICO

Population

24 Dutch families with congenital long QT syndrome (cLQTS)

Intervention

Genetic screening for KCNQ1 and HERG mutations

Outcome

Identification of missense mutations in KCNQ1 and HERG genessurrogate

Genetic screening of Dutch LQTS families identified eight novel missense mutations in KCNQ1 and HERG, emphasizing the value of DNA analysis to identify asymptomatic carriers at risk for life-threatening arrhythmias.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Congenital long QT syndrome (cLQTS) is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncopes, seizure, or sudden death. LQTS can occur either as an autosomal dominant (Romano Ward) or as an autosomal recessive disorder (Jervell and Lange-Nielsen syndrome). Mutations in at least five genes have been associated with the LQTS. Four genes, encoding cardiac ion channels, have been identified. The most common forms of LQTS are due to mutations in the potassium-channel genes KCNQ1 and HERG. We have screened 24 Dutch LQTS families for mutations in KCNQ1 and HERG. Fourteen missense mutations were identified. Eight of these missense mutations were novel: three in KCNQ1 and five in HERG. Novel missense mutations in KCNQ1 were Y184S, S373P, and W392R and novel missense mutations in HERG were A558P, R582C, G604S, T613M, and F640L. The KCNQ1 mutation G189R and the HERG mutation R582C were detected in two families. The pathogenicity of the mutations was based on segregation in families, absence in control individuals, the nature of the amino acid substitution, and localization in the protein. Genotype-phenotype studies indicated that auditory stimuli as trigger of cardiac events differentiate LQTS2 and LQTS1. In LQTS1, exercise was the predominant trigger. In addition, a number of asymptomatic gene defect carriers were identified. Asymptomatic carriers are still at risk of the development of life-threatening arrhythmias, underlining the importance of DNA analyses for unequivocal diagnosis of patients with LQTS

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Cite This Study

Jongbloed et al. (Fri,) reported a other. Fourteen missense mutations in KCNQ1 and HERG were found in Dutch LQTS families, including eight novel mutations affecting disease diagnosis and phenotype triggers.

synapsesocial.com/papers/69a3d6eaec16d51705d2da0a https://doi.org/https://doi.org/10.1002/(sici)1098-1004(1999)13:4

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