Mutational spectrum of congenital long QT syndrome in Turkey; identification of 12 novel mutations across KCNQ1, KCNH2, SCN5A, KCNJ2, CACNA1C, and CALM1.
J Cardiovasc Electrophysiol
; 33(2): 262-273, 2022 02.
Article
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| MEDLINE
| ID: mdl-34860437
ABSTRACT
INTRODUCTION:
Long QT syndrome (LQTS) is of great importance as it is the most common cause of sudden cardiac death in childhood. The diagnosis is made by the prolongation of the QTc interval on the electrocardiography. However, clinical heterogeneity and nondiagnostic QTc intervals may cause a delay in the diagnosis. In such cases, genetic tests such as next-generation sequencing (NGS) panel analysis enable a definitive diagnosis. We present the first study that aimed to expand the LQTS's mutational spectrum by NGS panel analysis from Turkey.METHODS:
Fifty-seven unrelated patients with clinically diagnosed LQTS were investigated using an NGS panel that includes six LQTS-related genes. Clinical aspects, outcome, and molecular analysis results were reviewed.RESULTS:
Pathogenic (53%)/likely pathogenic (23%)/variant of unknown significance (4%) variants were detected in any of the genes examined in 79% of the patients. Among all detected variants, KCNQ1(71%) was the most common gene, followed by SCN5A (11%), KCNH2 (10%), CALM1 (5%), and CACNA1C (3%). Twelve novel variants were detected. Among the variants in KCNQ1, the c.1097G>A variant was present in 42% of patients. This variant also composed 31% of the variants detected in all of the genes.CONCLUSION:
Our study expands the spectrum of the variations associated with LQTS with twelve novel variants in five genes. And also it draws attention to the frequency of the KCNQ1 c.1097G>A variant and forms the basis for new studies to determine the possible founder effect in the Turkish population. Furthermore, identifying new variants and clinical findings has importance in elaborating the roles of related genes in pathophysiology and determining the variable expression and incomplete penetration rates in this syndrome.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Síndrome de QT Prolongado
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Canales de Potasio de Rectificación Interna
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
País/Región como asunto:
Asia
Idioma:
En
Revista:
J Cardiovasc Electrophysiol
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
FISIOLOGIA
Año:
2022
Tipo del documento:
Article