A Novel SCN5A Variant Causes Temperature-Sensitive Loss Of Function in a Family with Symptomatic Brugada Syndrome, Cardiac Conduction Disease, and Sick Sinus Syndrome.
Cardiology
; 146(6): 754-762, 2021.
Article
en En
| MEDLINE
| ID: mdl-34348284
ABSTRACT
INTRODUCTION:
Brugada syndrome (BrS) is an inherited arrhythmia syndrome associated with an increased risk of sudden cardiac death. SCN5A is the most important disease-modifying gene for BrS, but many SCN5A variants have not been functionally characterized. Furthermore, the temperature dependency of SCN5A is only rarely explored in in vitro analyses.METHODS:
The clinical phenotype of the affected family was assessed by medical history, ECGs and ajmaline challenge. Whole-cell patch clamp recordings were performed on HEK 293T cells expressing Nav1.5-G1712S, a novel SCN5A variant found in the symptomatic family.RESULTS:
Three male family members had experienced sudden cardiac death, sudden cardiac arrest, and rhythmogenic syncopes. Beside a positive ajmaline challenge with demarcation of a Brugada type 1 ECG, 1 patient also showed evidence of symptomatic cardiac conduction disease and sick sinus syndrome (SSS). In patch clamp analyses, Nav1.5-G1712S generated reduced peak currents as compared to the wild type. At body temperature, Nav1.5-G1712S additionally exhibited an enhanced slow inactivation and an impaired recovery from inactivation.CONCLUSION:
We conclude that G1712S is a pathogenic SCN5A loss-of function mutation at physiological temperature associated with an overlapping presentation of BrS, SSS, and cardiac conduction disease.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Síndrome del Seno Enfermo
/
Síndrome de Brugada
/
Canal de Sodio Activado por Voltaje NAV1.5
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
Cardiology
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania