FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3183283602> ?p ?o ?g. }

• W3183283602 endingPage "S196" @default.
• W3183283602 startingPage "S195" @default.
• W3183283602 abstract "BackgroundBrugada syndrome (BrS) is a severe inherited arrhythmia syndrome which can be unmasked by fever.ObjectiveTo describe the clinical features and unique characteristics of SCN5A mutations contributing to the development off ever-induced BrS.MethodsThe clinical analysis was performed in 134 probands diagnosed with fever-induced BrS, including 59 patients who received next-generation genetic sequencing. We employed a biophysics-based computational protocol to investigate whether protein structure destabilization contributes to Nav1.5 variant-mediated fever-induced BrS.ResultsAmong all cases enrolled, the symptoms at diagnosis were syncope in 26 (19.40%) and major arrhythmic events (MAE) in 16 (11.94%). SCN5A variant carriers were significantly younger than probands free of SCN5A variants. Multivariate analysis indicated that younger age, Caucasian ethnicity, family history of SCD, and wider Tpeak-Tend interval were independent predictors of MAE. Compared with a historical cohort of non-fever BrS probands carrying SCN5A variants, carriers with fever-induced BrS were prone to MAE at a younger age, and had a higher proportion of variants localizing at the interdomain linkers. Modeling result showed that most variants are destabilizing when temperature increases, suggesting that Nav1.5 structure destabilization is the cause of fever-induced BrS associated with SCN5A variants.ConclusionIn our cohort, SCN5A variant carriers with fever-induced BrS present at a younger age and harbor SCN5A variants predominantly localized to interdomain linker regions of Nav1.5. These SCN5A variants typically induce destabilization of Nav1.5 structure at higher body temperatures. Patients with SCN5A mutations present within interdomain linker regions may warrant more aggressive monitoring and management of fever. BackgroundBrugada syndrome (BrS) is a severe inherited arrhythmia syndrome which can be unmasked by fever. Brugada syndrome (BrS) is a severe inherited arrhythmia syndrome which can be unmasked by fever. ObjectiveTo describe the clinical features and unique characteristics of SCN5A mutations contributing to the development off ever-induced BrS. To describe the clinical features and unique characteristics of SCN5A mutations contributing to the development off ever-induced BrS. MethodsThe clinical analysis was performed in 134 probands diagnosed with fever-induced BrS, including 59 patients who received next-generation genetic sequencing. We employed a biophysics-based computational protocol to investigate whether protein structure destabilization contributes to Nav1.5 variant-mediated fever-induced BrS. The clinical analysis was performed in 134 probands diagnosed with fever-induced BrS, including 59 patients who received next-generation genetic sequencing. We employed a biophysics-based computational protocol to investigate whether protein structure destabilization contributes to Nav1.5 variant-mediated fever-induced BrS. ResultsAmong all cases enrolled, the symptoms at diagnosis were syncope in 26 (19.40%) and major arrhythmic events (MAE) in 16 (11.94%). SCN5A variant carriers were significantly younger than probands free of SCN5A variants. Multivariate analysis indicated that younger age, Caucasian ethnicity, family history of SCD, and wider Tpeak-Tend interval were independent predictors of MAE. Compared with a historical cohort of non-fever BrS probands carrying SCN5A variants, carriers with fever-induced BrS were prone to MAE at a younger age, and had a higher proportion of variants localizing at the interdomain linkers. Modeling result showed that most variants are destabilizing when temperature increases, suggesting that Nav1.5 structure destabilization is the cause of fever-induced BrS associated with SCN5A variants. Among all cases enrolled, the symptoms at diagnosis were syncope in 26 (19.40%) and major arrhythmic events (MAE) in 16 (11.94%). SCN5A variant carriers were significantly younger than probands free of SCN5A variants. Multivariate analysis indicated that younger age, Caucasian ethnicity, family history of SCD, and wider Tpeak-Tend interval were independent predictors of MAE. Compared with a historical cohort of non-fever BrS probands carrying SCN5A variants, carriers with fever-induced BrS were prone to MAE at a younger age, and had a higher proportion of variants localizing at the interdomain linkers. Modeling result showed that most variants are destabilizing when temperature increases, suggesting that Nav1.5 structure destabilization is the cause of fever-induced BrS associated with SCN5A variants. ConclusionIn our cohort, SCN5A variant carriers with fever-induced BrS present at a younger age and harbor SCN5A variants predominantly localized to interdomain linker regions of Nav1.5. These SCN5A variants typically induce destabilization of Nav1.5 structure at higher body temperatures. Patients with SCN5A mutations present within interdomain linker regions may warrant more aggressive monitoring and management of fever. In our cohort, SCN5A variant carriers with fever-induced BrS present at a younger age and harbor SCN5A variants predominantly localized to interdomain linker regions of Nav1.5. These SCN5A variants typically induce destabilization of Nav1.5 structure at higher body temperatures. Patients with SCN5A mutations present within interdomain linker regions may warrant more aggressive monitoring and management of fever." @default.
• W3183283602 created "2021-08-02" @default.
• W3183283602 creator A5005749391 @default.
• W3183283602 creator A5017645655 @default.
• W3183283602 creator A5020376217 @default.
• W3183283602 creator A5043075532 @default.
• W3183283602 creator A5045710602 @default.
• W3183283602 creator A5047279922 @default.
• W3183283602 creator A5051017957 @default.
• W3183283602 creator A5054318800 @default.
• W3183283602 creator A5055227838 @default.
• W3183283602 creator A5056355876 @default.
• W3183283602 creator A5063446960 @default.
• W3183283602 creator A5075234540 @default.
• W3183283602 creator A5076417856 @default.
• W3183283602 creator A5079305432 @default.
• W3183283602 creator A5079470936 @default.
• W3183283602 creator A5079751880 @default.
• W3183283602 creator A5081972026 @default.
• W3183283602 creator A5087202559 @default.
• W3183283602 date "2021-08-01" @default.
• W3183283602 modified "2023-10-16" @default.
• W3183283602 title "B-PO03-018 CLINICAL CHARACTERISTICS AND ELECTROPHYSIOLOGIC PROPERTIES OF SCN5A VARIANTS IN FEVER-INDUCED BRUGADA SYNDROME" @default.
• W3183283602 doi "https://doi.org/10.1016/j.hrthm.2021.06.494" @default.
• W3183283602 hasPublicationYear "2021" @default.
• W3183283602 type Work @default.
• W3183283602 sameAs 3183283602 @default.
• W3183283602 citedByCount "0" @default.
• W3183283602 crossrefType "journal-article" @default.
• W3183283602 hasAuthorship W3183283602A5005749391 @default.
• W3183283602 hasAuthorship W3183283602A5017645655 @default.
• W3183283602 hasAuthorship W3183283602A5020376217 @default.
• W3183283602 hasAuthorship W3183283602A5043075532 @default.
• W3183283602 hasAuthorship W3183283602A5045710602 @default.
• W3183283602 hasAuthorship W3183283602A5047279922 @default.
• W3183283602 hasAuthorship W3183283602A5051017957 @default.
• W3183283602 hasAuthorship W3183283602A5054318800 @default.
• W3183283602 hasAuthorship W3183283602A5055227838 @default.
• W3183283602 hasAuthorship W3183283602A5056355876 @default.
• W3183283602 hasAuthorship W3183283602A5063446960 @default.
• W3183283602 hasAuthorship W3183283602A5075234540 @default.
• W3183283602 hasAuthorship W3183283602A5076417856 @default.
• W3183283602 hasAuthorship W3183283602A5079305432 @default.
• W3183283602 hasAuthorship W3183283602A5079470936 @default.
• W3183283602 hasAuthorship W3183283602A5079751880 @default.
• W3183283602 hasAuthorship W3183283602A5081972026 @default.
• W3183283602 hasAuthorship W3183283602A5087202559 @default.
• W3183283602 hasBestOaLocation W31832836021 @default.
• W3183283602 hasConcept C104317684 @default.
• W3183283602 hasConcept C126322002 @default.
• W3183283602 hasConcept C164705383 @default.
• W3183283602 hasConcept C188997412 @default.
• W3183283602 hasConcept C2777382798 @default.
• W3183283602 hasConcept C501734568 @default.
• W3183283602 hasConcept C54355233 @default.
• W3183283602 hasConcept C71924100 @default.
• W3183283602 hasConcept C72563966 @default.
• W3183283602 hasConcept C86803240 @default.
• W3183283602 hasConceptScore W3183283602C104317684 @default.
• W3183283602 hasConceptScore W3183283602C126322002 @default.
• W3183283602 hasConceptScore W3183283602C164705383 @default.
• W3183283602 hasConceptScore W3183283602C188997412 @default.
• W3183283602 hasConceptScore W3183283602C2777382798 @default.
• W3183283602 hasConceptScore W3183283602C501734568 @default.
• W3183283602 hasConceptScore W3183283602C54355233 @default.
• W3183283602 hasConceptScore W3183283602C71924100 @default.
• W3183283602 hasConceptScore W3183283602C72563966 @default.
• W3183283602 hasConceptScore W3183283602C86803240 @default.
• W3183283602 hasIssue "8" @default.
• W3183283602 hasLocation W31832836021 @default.
• W3183283602 hasOpenAccess W3183283602 @default.
• W3183283602 hasPrimaryLocation W31832836021 @default.
• W3183283602 hasRelatedWork W2053766426 @default.
• W3183283602 hasRelatedWork W2597940648 @default.
• W3183283602 hasRelatedWork W2600182461 @default.
• W3183283602 hasRelatedWork W2693311789 @default.
• W3183283602 hasRelatedWork W2893783387 @default.
• W3183283602 hasRelatedWork W4206264495 @default.
• W3183283602 hasRelatedWork W4235569942 @default.
• W3183283602 hasRelatedWork W4241982233 @default.
• W3183283602 hasRelatedWork W4250742818 @default.
• W3183283602 hasRelatedWork W4296908158 @default.
• W3183283602 hasVolume "18" @default.
• W3183283602 isParatext "false" @default.
• W3183283602 isRetracted "false" @default.
• W3183283602 magId "3183283602" @default.
• W3183283602 workType "article" @default.