A homozygous SCN5A mutation associated with atrial standstill and sudden death
| Autor: | Frank Cecchin, Ivan Gando, Reina Bianca Tan, Lei Bu, William A. Coetzee |
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| Rok vydání: | 2018 |
| Předmět: |
Proband
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Atrial standstill business.industry Mutant General Medicine 030204 cardiovascular system & hematology medicine.disease Asymptomatic Ryanodine receptor 2 Sudden death Sick sinus syndrome 03 medical and health sciences 0302 clinical medicine Internal medicine cardiovascular system Cardiology Medicine cardiovascular diseases Patch clamp medicine.symptom Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery |
| Zdroj: | Pacing and Clinical Electrophysiology. 41:1036-1042 |
| ISSN: | 0147-8389 |
| Popis: | Background Atrial standstill is an arrhythmogenic condition characterized by the absence of spontaneous electrical and mechanical atrial activity or in response to stimulation. There are few reported familial cases which have been associated with SCN5A mutations cosegregating with GJA5 or RYR2; however, isolated SCN5A mutations are rare. Objective The purpose of this study was to determine the clinical and biophysical consequence of a novel SCN5A mutation identified in a family with progressive atrial standstill and sudden death. Methods The family of a sporadic case of congenital atrial standstill underwent genetic screening. Human Embryonic Kidney 293 cells were transfected with wild-type (WT) or mutant SCN5A cDNAs. Biophysical properties were studied using whole-cell using patch clamp methods. Results A novel homozygous SCN5A mutation, p.V1340L, was identified in the proband and her sister. The proband had complete atrial standstill whereas the sister had partial atrial standstill. Heterozygous mutations were identified in the mother, father, and brother. All three had normal sinus rhythm and were asymptomatic. The mutant Nav1.5(V1340L) reduced Nav1.5 current density as well as showed a depolarizing shift in the voltage-dependent steady-state activation (WT: -35.3 ± 1.62 mV; V1340L: -22.4 ± 2.59 mV; P = 0.001). Conclusions A homozygous loss-of-function SCN5A mutation likely results in atrial standstill and sudden death due to suppression of initiation of action potential. |
| Databáze: | OpenAIRE |
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