Mutation-Specific Risk in Two Genetic Forms of Type 3 Long QT Syndrome

Judy F. Liu, Arthur J. Moss, Christian Jons, Jesaia Benhorin, Peter J. Schwartz, Carla Spazzolini, Lia Crotti, Michael John Ackerman, Scott McNitt, Jennifer L. Robinson, Ming Qi, Ilan Goldenberg, Wojciech Zareba

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Abstract

The clinical course of patients with 2 relatively common long QT syndrome type 3 mutations has not been well described. In the present study, we investigated the mutational-specific risk in patients with deletional (ΔKPQ) and missense (D1790G) mutations involving the SCN5A gene. The study population involved 50 patients with the ΔKPQ mutation and 35 patients with the D1790G mutation. The cumulative probability of a first cardiac event (syncope, aborted cardiac arrest, or long QT syndrome-related sudden death) was evaluated using the Kaplan-Meier method. The Cox proportional hazards survivorship model was used to determine the independent contribution of clinical and genetic factors to the first occurrence of cardiac events from birth through 40 years of age. The Andersen-Gill proportional intensity regression model was used to analyze the factors associated with recurrent syncope. Patients with a ΔKPQ mutation had a significantly greater probability of a first cardiac event from birth through 40 years of age (34%) than those with the D1790G mutation (20%; p <0.001). Multivariate analysis demonstrated an increased risk of cardiac events among ΔKPQ carriers compared to D1790G carriers (hazard ratio 2.42, p <0.0001) after adjustment for gender and QTc duration. Patients with ΔKPQ mutations also had an increased risk of recurrent syncope (hazard ratio 5.20, p <0.001). In conclusion, the clinical course of patients with long QT syndrome type with ΔKPQ mutations was shown to be more virulent than those with D1790G mutations, and this effect was independent of QTc duration. The findings highlight the importance of knowing the specific mutation in risk stratification of patients with long QT syndrome type 3.

Original languageEnglish (US)
Pages (from-to)210-213
Number of pages4
JournalAmerican Journal of Cardiology
Volume105
Issue number2
DOIs
StatePublished - Jan 15 2010

Fingerprint

Mutation
Syncope
Long QT Syndrome
Parturition
Long QT syndrome type 3
Missense Mutation
Sudden Death
Heart Arrest
Proportional Hazards Models
Statistical Factor Analysis
Multivariate Analysis
Survival Rate
Population
Genes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Liu, J. F., Moss, A. J., Jons, C., Benhorin, J., Schwartz, P. J., Spazzolini, C., ... Zareba, W. (2010). Mutation-Specific Risk in Two Genetic Forms of Type 3 Long QT Syndrome. American Journal of Cardiology, 105(2), 210-213. https://doi.org/10.1016/j.amjcard.2009.08.676

Mutation-Specific Risk in Two Genetic Forms of Type 3 Long QT Syndrome. / Liu, Judy F.; Moss, Arthur J.; Jons, Christian; Benhorin, Jesaia; Schwartz, Peter J.; Spazzolini, Carla; Crotti, Lia; Ackerman, Michael John; McNitt, Scott; Robinson, Jennifer L.; Qi, Ming; Goldenberg, Ilan; Zareba, Wojciech.

In: American Journal of Cardiology, Vol. 105, No. 2, 15.01.2010, p. 210-213.

Research output: Contribution to journalArticle

Liu, JF, Moss, AJ, Jons, C, Benhorin, J, Schwartz, PJ, Spazzolini, C, Crotti, L, Ackerman, MJ, McNitt, S, Robinson, JL, Qi, M, Goldenberg, I & Zareba, W 2010, 'Mutation-Specific Risk in Two Genetic Forms of Type 3 Long QT Syndrome', American Journal of Cardiology, vol. 105, no. 2, pp. 210-213. https://doi.org/10.1016/j.amjcard.2009.08.676
Liu JF, Moss AJ, Jons C, Benhorin J, Schwartz PJ, Spazzolini C et al. Mutation-Specific Risk in Two Genetic Forms of Type 3 Long QT Syndrome. American Journal of Cardiology. 2010 Jan 15;105(2):210-213. https://doi.org/10.1016/j.amjcard.2009.08.676
Liu, Judy F. ; Moss, Arthur J. ; Jons, Christian ; Benhorin, Jesaia ; Schwartz, Peter J. ; Spazzolini, Carla ; Crotti, Lia ; Ackerman, Michael John ; McNitt, Scott ; Robinson, Jennifer L. ; Qi, Ming ; Goldenberg, Ilan ; Zareba, Wojciech. / Mutation-Specific Risk in Two Genetic Forms of Type 3 Long QT Syndrome. In: American Journal of Cardiology. 2010 ; Vol. 105, No. 2. pp. 210-213.
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abstract = "The clinical course of patients with 2 relatively common long QT syndrome type 3 mutations has not been well described. In the present study, we investigated the mutational-specific risk in patients with deletional (ΔKPQ) and missense (D1790G) mutations involving the SCN5A gene. The study population involved 50 patients with the ΔKPQ mutation and 35 patients with the D1790G mutation. The cumulative probability of a first cardiac event (syncope, aborted cardiac arrest, or long QT syndrome-related sudden death) was evaluated using the Kaplan-Meier method. The Cox proportional hazards survivorship model was used to determine the independent contribution of clinical and genetic factors to the first occurrence of cardiac events from birth through 40 years of age. The Andersen-Gill proportional intensity regression model was used to analyze the factors associated with recurrent syncope. Patients with a ΔKPQ mutation had a significantly greater probability of a first cardiac event from birth through 40 years of age (34{\%}) than those with the D1790G mutation (20{\%}; p <0.001). Multivariate analysis demonstrated an increased risk of cardiac events among ΔKPQ carriers compared to D1790G carriers (hazard ratio 2.42, p <0.0001) after adjustment for gender and QTc duration. Patients with ΔKPQ mutations also had an increased risk of recurrent syncope (hazard ratio 5.20, p <0.001). In conclusion, the clinical course of patients with long QT syndrome type with ΔKPQ mutations was shown to be more virulent than those with D1790G mutations, and this effect was independent of QTc duration. The findings highlight the importance of knowing the specific mutation in risk stratification of patients with long QT syndrome type 3.",
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