Fever Associated with Gastrointestinal Shigellosis Unmasks Probable Brugada Syndrome

Makaryus, John N.; Verbsky, Jennifer; Schwartz, S. N.; Slotwiner, David J.

doi:10.1155/2009/492031

Cited by 6 publications

(6 citation statements)

References 11 publications

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“…In patient 1, VF was induced with programmed stimulation applied to the RVOT. In the case of patient 2, aborted SCD occurred in conjunction with diarrhea and fever, previously reported triggers, 19, 20 and generally associated with SCN5A- mediated BrS. 21 No mutation in SCN5A was found in this patient.…”

Section: Discussionsupporting

confidence: 50%

A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na 1.5 and K 4.3 channel currents

Hu¹,

et al. 2012

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BACKGROUND Cardiac sodium channel β-subunit mutations have been associated with several inherited cardiac arrhythmia syndromes. OBJECTIVE To identify and characterize variations in SCN1Bb associated with Brugada (BrS) and sudden infant death syndromes (SIDS). METHODS AND RESULTS Patient 1 was a 44-y/o male with an ajmaline-induced Type-1 ST-segment elevation in V1 and V2 supporting the diagnosis of BrS. Patient 2 was a 62-y/o female displaying a coved-type BrS ECG who developed cardiac arrest during fever. Patient 3 was a 4-m/o female SIDS case. All known exons and intron borders of BrS and SIDS susceptibility genes were amplified and sequenced in both directions. A R214Q variant was detected in exon 3A of SCN1Bb (Navβ1B) in all three probands, but not in any other gene previously associated with BrS or SIDS. R214Q was identified in 4 of 807 ethnically-matched healthy controls (0.50%). Wild type (WT) and mutant genes were expressed in TSA201 cells and studied using whole-cell patch-clamp and co-immunoprecipitation techniques. Co-expression of SCN5A/WT+SCN1Bb/R214Q resulted in peak sodium channel current (INa) 56.5% smaller compared to SCN5A/WT+SCN1Bb/WT ( n=11–12, p<0.05 ). Co-expression of KCND3/WT+SCN1Bb/R214Q induced a Kv4.3 current (Ito) 70.6% greater compared with KCND3/WT+SCN1Bb/WT(n=10–11, p<0.01). Co-immunoprecipitation indicated structural association between Navβ1B and Nav1.5 and Kv4.3. CONCLUSION Our results suggest that R214Q variation in SCN1Bb is a functional polymorphism that may serve as a modifier of the substrate responsible for Brugada or SIDS phenotypes via a combined loss of function of INa and gain of function of Ito.

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Section: Discussionsupporting

confidence: 50%

A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na 1.5 and K 4.3 channel currents

Hu¹,

et al. 2012

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“…; Makaryus et al . ). BrS1 may be unmasked by decreases in plasma pH, changes in body core temperatures, and pharmacological agents that block sodium channels (Mok et al .…”

Section: Introductionmentioning

confidence: 97%

Differential thermosensitivity in mixed syndrome cardiac sodium channel mutants

Abdelsayed

Peters

Ruben

2015

The Journal of Physiology

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Key pointsr The E1784K mixed syndrome mutant of the cardiac voltage-gated sodium channel, Na V 1.5, responds differently to temperature changes compared to the R1193Q mutant and wild-type (WT) Na V 1.5.r In E1784K, elevated temperature causes a larger increase in persistent current; there is also an increase in use-dependent inactivation at 1 Hz, which is not apparent at 3 Hz.r WT Na V 1.5 and R1193Q channels respond similarly to temperature changes. r Action potential modelling (from extrapolated temperature coefficient (Q 10 )values) predicts the effects of differential temperature sensitivity on the cardiac action potential: greater attenuation of the epicardial action potential occurs in E1784K as temperature shifts from hypothermic to hyperthermic conditions, and when transient outward potassium currents are increased.r The results from the action potential model predict that, at febrile temperatures, E1784K channels results in a larger transmural voltage gradient.r Hyperthermia exacerbates the Brugada syndrome 1 (BrS1) phenotype, which may be arrhythmogenic in E1784K mutants.Abstract Cardiac arrhythmias are often associated with mutations in SCN5A the gene that encodes the cardiac paralogue of the voltage-gated sodium channel, Na V 1.5. The Na V 1.5 mutants R1193Q and E1784K give rise to both long QT and Brugada syndromes. Various environmental factors, including temperature, may unmask arrhythmia. We sought to determine whether temperature might be an arrhythmogenic trigger in these two mixed syndrome mutants. Whole-cell patch clamp was used to measure the biophysical properties of Na V 1.5 WT, E1784K and R1193Q mutants. Recordings were performed using Chinese hamster ovary (CHOk1) cells transiently transfected with the Na V 1.5 α subunit (WT, E1784K, or R1193Q), β1 subunit, and eGFP. The channels' voltage-dependent and kinetic properties were measured at three different temperatures: 10ºC, 22ºC, and 34ºC. The E1784K mutant is more thermosensitive than either WT or R1193Q channels. When temperature is elevated from 22°C to 34°C, there is a greater increase in late I Na and use-dependent inactivation in E1784K than in WT or R1193Q. However, when temperature is lowered to 10°C, the two mutants show a decrease in channel availability. Action potential modelling using Q 10 fit values, extrapolated to physiological and febrile temperatures, show a larger transmural voltage gradient in E1784K compared to R1193Q and WT with hyperthermia. The E1784K mutant is more thermosensitive than WT or R1193Q channels. This enhanced thermosensitivity may be a mechanism for arrhythmogenesis in patients with E1784K sodium channels.

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“…Temperature-dependent gating changes in these sodium channels have been identified, suggesting a possible molecular mechanism for the appearance of the Brugada ECG patterns in febrile patients 5. Previous reports have documented Brugada ECG pattern arising in the context of a febrile illness such as pneumonia,6 bacteraemia,7 8 viral infections,8 9 gastrointestinal infections10 and mastitis 11…”

Section: Discussionmentioning

confidence: 99%

The management of Brugada syndrome unmasked by fever in a patient with cellulitis

2013

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Fever Associated with Gastrointestinal Shigellosis Unmasks Probable Brugada Syndrome

Cited by 6 publications

References 11 publications

A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na 1.5 and K 4.3 channel currents

A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na 1.5 and K 4.3 channel currents

Differential thermosensitivity in mixed syndrome cardiac sodium channel mutants

The management of Brugada syndrome unmasked by fever in a patient with cellulitis

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