Stop-codon and C-terminal nonsense mutations are associated with a lower risk of cardiac events in patients with long QT syndrome type 1

Heart Rhythm : the Official Journal of the Heart Rhythm Society
Martin H RuwaldCoeli M Lopes

Abstract

In long QT syndrome type 1 (LQT1), the location and type of mutations have been shown to affect the clinical outcome. Although haploinsufficiency, including stop-codon and frameshift mutations, has been associated with a lower risk of cardiac events in patients with LQT1, nonsense mutations have been presumed functionally equivalent. The purpose of this study was to evaluate clinical differences between patients with nonsense mutations. The study sample comprised 1090 patients with genetically confirmed mutations. Patients were categorized into 5 groups, depending on mutation type and location: missense not located in the high-risk cytoplasmic loop (c-loop) (n = 698), which is used as reference; missense c-loop (n = 192); stop-codon (n = 67); frameshift (n = 39); and others (n = 94). The primary outcome was a composite end point of syncope, aborted cardiac arrest, and long QT syndrome-related death (cardiac events). Outcomes were evaluated using the multivariate Cox proportional hazards regression analysis. Standard patch clamp techniques were used. Compared to patients with missense non-c-loop mutations, the risk of cardiac events was reduced significantly in patients with stop-codon mutations (hazard ratio [HR] 0.57; 95% conf...Continue Reading

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Citations

Nov 4, 2016·Physiological Reviews·M S BohnenR S Kass
Oct 24, 2017·Current Opinion in Cardiology·Clauden LouisJeffrey M Vinocur
Oct 26, 2018·Circulation. Genomic and Precision Medicine·Michael MackleyElizabeth Ormondroyd
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Jul 17, 2018·Heart and Vessels·Xiao-Meng ChenYi-Gang Li
May 17, 2021·Journal of Cardiovascular Electrophysiology·Jayson R BamanJane E Wilcox

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