Online ISSN: 3007-0244,
Print ISSN:  2410-4280
Introduction. Cardiac arrhythmias are the most common among the group of cardiovascular diseases (CVD), and have a risk of sudden cardiac death (SCD). Long QT syndrome (LQTS) is a heritable disease characterized by prolongation of the QT interval on an electrocardiogram (ECG), which often leads to syncope and SCD. Currently, identification of mutations in cardiac ion channel genes in patients with LQTS and recognition of genetic causes of the syndrome are actual in cardiology. Aim. To identify cardiac ion channel mutations in genes associated with long QT syndrome in Kazakhstani patients. Materials and methods. This study was designed as a cohort study. At present, our study has identified three patients with LQTS. Nevertheless, the recruitment of additional patients with LQTS for the study is ongoing. Illumina TruSight Cardio panel was used for genetic screening. The cardiopanel consists of 174 genes associated with cardiac disorders including LQTS. After a targeted sequencing, data analysis was carried out using the programs SureCall version (Agilent Technologies, Santa Clara, California, USA), ANNOVAR, GTK, bwa, bowtie, bow tie 2, VarScan, etc. Results. Clinically significant variants were found in patients with LQTS. Namely, in genes SCN5A (c.G5296A:p.E1766K) and KCNH2 (c.C662T:p.A221V). Both variants are pathogenic and cause CVDs, specifically LQTS. In addition, c.G3785A mutation (p.R1262Q), a variant of uncertain significance in SCN5A gene was detected in one patient. Although there is insufficient data to determine the role of the variant in development of the disease. Conclusions. Screening for mutations in cardiac ion channel genes in patients with LQTS revealed clinically significant mutations. This research will be useful for Kazakhstani patients with LQTS in evaluation of required genetic testing and reliable genetic guidance to prevent SCD and distinguish between various arrhythmias.
Ayaulym E. Chamoieva1, Madina R. Zhalbinova1, Zhanel Z. Mirmanova1, Saule E. Rakhimova1, Ayan S. Abdrakhmanov2,3, Ainur R. Akilzhanova1, 1 National Laboratory Astana, Nazarbayev University, Astana, Republic of Kazakhstan; 2 Medical University Astana, Department of Cardiology, Astana, Republic of Kazakhstan; 3 Medical Centre Hospital of President’s Affairs Administration of the Republic of Kazakhstan, Astana, Republic of Kazakhstan.
1. Ackerman M.J., Priori S.G., Willems S., Berul C., Brugada R., Calkins H., et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA) // Heart Rhythm. 2011. 8(8). P. 1308–39. 2. Alders M., Bikker H. Long QT Syndrome // Gene Reviews. 2003 Feb 20. Available from: / [Updated 2018 Feb 8]. 3. Bohnen M.S., Peng G., Robey S.H., Terrenoire C., Iyer V., Sampson K.J., Kass R.S. Molecular Pathophysiology of Congenital Long QT Syndrome // Physiological reviews. 2017. 97(1). P. 89–134. 4. Chen B., Tan L., Chen D., Wang X., Liu J., Huang X., Wang Y., Huang S., Mao F., Lian J. KCNH2A561V Heterozygous Mutation Inhibits KCNH2 Protein Expression via The Activation of UPR Mediated by ATF6 // Physiological research. 2023. 72(5). P. 621–631. 5. Crotti L., Odening K.E., Sanguinetti M.C. Heritable arrhythmias associated with abnormal function of cardiac potassium channels // Cardiovascular research. 2020. 116(9). P. 1542-1556. 6. Deschênes I., Baroudi G., Berthet M., Barde I., Chalvidan T., Denjoy I., Guicheney P., Chahine M. Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes // Cardiovascular research. 2000. 46(1). P. 55–65. 7. Garcia-Elias A., Benito B. Ion Channel Disorders and Sudden Cardiac Death // International journal of molecular sciences. 2018. 19(3). P. 692. 8. Giudicessi J.R., Ackerman M.J. Potassium-channel mutations and cardiac arrhythmias-diagnosis and therapy // Nat Rev Cardiol. 2012. 9(6). P. 319–32. 9. Giudicessi J.R., Wilde A.A., Ackerman M.J. The genetic architecture of long QT syndrome: a critical reappraisal // Trends in cardiovascular medicine. 2018. 28(7). P. 453-464. 10. Horner J.M., Kinoshita M., Webster T.L., Haglund C.M., Friedman P.A., Ackerman M.J. Implantable cardioverter defibrillator therapy for congenital long QT syndrome: a single-center experience // Heart Rhythm. 2010. 7. P. 1616–1622. 11. Ingles J., Semsarian C. Time to Rethink the Genetic Architecture of Long QT Syndrome // Circulation. 2020. 141(6). P. 440-443. 12. Kanatbaeva A.A. Prevention and treatment of cardiovascular diseases (AH, CHD) // Vestnik KazNMU. 2013. № 4(1). P. 139-141. [in Russian] 13. Koene R.J., Adkisson W.O., Benditt D.G. Syncope and the risk of sudden cardiac death: Evaluation, management, and prevention // Journal of arrhythmia. 2017. 33(6). P. 533-544. 14. Nerbonne J.M., Kass R.S. Molecular physiology of cardiac repolarization // Physiological reviews. 2005. 85(4). P. 1205–53. 15. Perez M.V., Kumarasamy N.A., Owens D.K., Wang P.J., Hlatky M.A. Cost-effectiveness of genetic testing in family members of patients with long-QT syndrome // Circulation: Cardiovascular Quality and Outcomes. 2011. 4(1). P. 76-84. 16. Priori S.G., Wilde A.A., Horie M., Cho Y., Behr E.R., Berul C., Blom N., Brugada J., Chiang C.E., Huikuri H., Kannankeril P. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: Document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013 // Heart Rhythm. 2013. 10. P. 1932–19639. 17. Richards S., Aziz N., Bale S., Bick D., Das S., Gastier-Foster J., Grody W.W., Hegde M., Lyon E., Spector, E., Voelkerding K. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology // Genetics in medicine: official journal of the American College of Medical Genetics. 2015. 17(5). P. 405–424. 18. Schwartz P.J., Crotti L., Insolia R. Long-QT syndrome: from genetics to management // Circulation. Arrhythmia and electrophysiology. 2012. 5(4). P. 868–877. 19. Schwartz P.J., et al. Impact of genetics on the clinical management of channelopathies // Journal of the American College of Cardiology. 2013. 62(3). P. 169-180. 20. Schwartz P.J., Spazzolini C., Priori S.G., Crotti L., Vicentini A., Landolina M., Gasparini M., Wilde A.A., Knops R.E., Denjoy I., Toivonen L. Who are the long-QT syndrome patients who receive an implantable cardioverter-defibrillator and what happens to them? Data from the European Long-QT Syndrome Implantable Cardioverter-Defibrillator (LQTS ICD) Registry // Circulation. 2010. 122. P. 1272–1282 21. Taggart N.W., Haglund C.M., Tester D.J., Ackerman M.J. Diagnostic miscues in congenital long-QT syndrome // Circulation. 2007. 115(20). P. 2613–20. 22. Tester D.J., Ackerman M.J. Genetics of long QT syndrome // Methodist DeBakey cardiovascular journal. 2014. 10(1). P. 29–33. 23. Tester D.J., Ackerman M.J. Genetic testing for potentially lethal highly treatable inherited cardiomyopathies/channelopathies in clinical practice // Circulation. 2011. 123(9). P. 1021–37. 24. Tester D.J., Will ML, Haglund C.M., Ackerman M.J. Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing // Heart Rhythm. 2005. 2(5). P. 507–17. 25. The Genome Aggregation Database (gnom AD) [Electronic resource] URL: (date of application: 22.01.2024) 26. Wilde A.A., Amin A.S., Postema P.G. Diagnosis, management and therapeutic strategies for congenital long QT syndrome // Heart. 2022. 108(5). P. 332–338. 27. World Health Organization (WHO) [Electronic resource] URL: (date of application: 17.05.2017). 28. Zipes D.P., Camm A.J., Borggrefe M., Buxton A.E., Chaitman B., Fromer M., Gregoratos G., Klein G., Moss A.J., Myerburg R.J., et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death // Circulation. 2006. 114. P. e385–e484.
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Chamoieva A.E., Zhalbinova M.R., Mirmanova Zh.Z., Rakhimova S.E., Abdrakhmanov A.S., Akilzhanova A.R. Mutations in cardiac ion channel genes in kazakhstani patients with long QT syndrome // Nauka i Zdravookhranenie [Science & Healthcare]. 2024, (Vol.26) 1, pp. 7-14. doi 10.34689/SH.2024.26.1.001

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