The Spectrum of SCN5A Gene Mutations in Spanish Brugada Syndrome Patients

SCN5A gene mutations can lead to ion channel defects which can cause cardiac conduction disturbances. In the presence of specific ECG characteristics, this mutation is called Brugada syndrome. Many drugs are associated with adverse events, making anesthesia in patients with SCN5A gene mutations or Brugada syndrome challenging. In this case report, we describe a pregnant patient with this mutation who received epidural analgesia using low dose ropivacaine and sufentanil during labour.

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Structural Heart Disease, SCN5A Gene Mutations, and Brugada Syndrome

Circulation ◽

10.1161/circulationaha.105.587147 ◽

2005 ◽

Vol 112 (24) ◽

pp. 3672-3674 ◽

Cited By ~ 13

Author(s):

Jeffrey E. Saffitz

Keyword(s):

Heart Disease ◽

Brugada Syndrome ◽

Gene Mutations ◽

Structural Heart Disease ◽

Scn5a Gene

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Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome

Cardiovascular Research ◽

10.1016/s0008-6363(99)00350-8 ◽

1999 ◽

Vol 44 (3) ◽

pp. 507-517 ◽

Cited By ~ 121

Author(s):

M Rook

Keyword(s):

Sodium Channel ◽

Brugada Syndrome ◽

Gene Mutations ◽

Channel Kinetics ◽

Cardiac Sodium Channel ◽

Scn5a Gene

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Genetic Characteristics and Transcriptional Regulation of Sodium Channel Related Genes in Chinese Patients With Brugada Syndrome

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.714844 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ziguan Zhang ◽

Hongwei Chen ◽

Wenbo Chen ◽

Zhenghao Zhang ◽

Runjing Li ◽

...

Keyword(s):

Transcriptional Regulation ◽

Brugada Syndrome ◽

Southern China ◽

Gene Mutations ◽

Northern China ◽

Chinese Patients ◽

Α Subunit ◽

Genetic Characteristics ◽

C Terminus ◽

Scn5a Gene

Objective: To investigate the genetic characteristics and transcriptional regulation of the SCN5A gene of Brugada syndrome (BrS) patients in China.Methods: Using PubMed, Medline, China National Knowledge Internet (CNKI), and Wanfang Database, Chinese patients with BrS who underwent SCN5A gene testing were studied.Results: A total of 27 suitable studies involving Chinese BrS patients who underwent the SCN5A gene test were included. A total of 55 SCN5A gene mutations/variations were reported in Chinese BrS patients, including 10 from southern China and 45 from northern China. Mutations/variations of BrS patients from southern China mostly occurred in the regions of the α-subunit of Nav1.5, including DIII (Domain III), DIV, DIII-DIV, C-terminus regions, and the 3'UTR region. Furthermore, we analyzed the post-transcriptional modifications (PTMs) throughout the Nav1.5 protein encoded by SCN5A and found that the PTM changes happened in 72.7% of BrS patients from southern China and 26.7% from northern China.Conclusions: SCN5A mutations/variations of BrS patients in southern China mostly occurred in the DIII-DIV to C-terminus region and the 3'-UTR region of the SCN5A gene, different from northern China. PTM changes were consistent with the mutation/variation distribution of SCN5A, which might be involved in the regulation of the pathogenesis of BrS patients.

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Novel SCN5A p.Val1667Asp Missense Variant Segregation and Characterization in a Family with Severe Brugada Syndrome and Multiple Sudden Deaths

International Journal of Molecular Sciences ◽

10.3390/ijms22094700 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4700

Author(s):

Michelle M. Monasky ◽

Emanuele Micaglio ◽

Giuseppe Ciconte ◽

Ilaria Rivolta ◽

Valeria Borrelli ◽

...

Keyword(s):

Genetic Testing ◽

Family History ◽

Risk Stratification ◽

Brugada Syndrome ◽

Electrophysiological Study ◽

Functional Characterization ◽

The Family ◽

Novel Variant ◽

History Of ◽

Scn5a Gene

Genetic testing in Brugada syndrome (BrS) is still not considered to be useful for clinical management of patients in the majority of cases, due to the current lack of understanding about the effect of specific variants. Additionally, family history of sudden death is generally not considered useful for arrhythmic risk stratification. We sought to demonstrate the usefulness of genetic testing and family history in diagnosis and risk stratification. The family history was collected for a proband who presented with a personal history of aborted cardiac arrest and in whom a novel variant in the SCN5A gene was found. Living family members underwent ajmaline testing, electrophysiological study, and genetic testing to determine genotype-phenotype segregation, if any. Patch-clamp experiments on transfected human embryonic kidney 293 cells enabled the functional characterization of the SCN5A novel variant in vitro. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.5000T>A (p.Val1667Asp) in the SCN5A gene, and demonstrate its segregation with a severe form of BrS and multiple sudden deaths. Functional data revealed a loss of function of the protein affected by the variant. These results provide the first disease association with this variant and demonstrate the usefulness of genetic testing for diagnosis and risk stratification in certain patients. This study also demonstrates the usefulness of collecting the family history, which can assist in understanding the severity of the disease in certain situations and confirm the importance of the functional studies to distinguish between pathogenic mutations and harmless genetic variants.

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Repeated molecular genetic analysis in Brugada syndrome revealed a novel disease-associated large deletion in the SCN5A gene

HeartRhythm Case Reports ◽

10.1016/j.hrcr.2016.02.008 ◽

2016 ◽

Vol 2 (3) ◽

pp. 261-264 ◽

Cited By ~ 2

Author(s):

Anders Krogh Broendberg ◽

Lisbeth Noerum Pedersen ◽

Jens Cosedis Nielsen ◽

Henrik Kjaerulf Jensen

Keyword(s):

Genetic Analysis ◽

Brugada Syndrome ◽

Molecular Genetic ◽

Large Deletion ◽

Molecular Genetic Analysis ◽

Scn5a Gene

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Comparing the SCN5A Gene Sequence and Expression in Three Different Brugada Syndrome Profiles of Patients: New Insights for Genotype-Phenotype Correlation

International Journal of Human Genetics ◽

10.31901/24566330.2020/20.03.727 ◽

2020 ◽

Vol 20 (03) ◽

Author(s):

Amel Haj Khelil

Keyword(s):

Brugada Syndrome ◽

Gene Sequence ◽

Phenotype Correlation ◽

Genotype Phenotype Correlation ◽

Scn5a Gene

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Abstract 5346: Regulation of Cardiac Na + Current by Pyridine Nucleotides: A Possible Explanation of Glycerol-3-Phosphate Dehydrogenase-Linked Brugada Syndrome

Circulation ◽

10.1161/circ.118.suppl_18.s_532-b ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Shamarendra Sanyal ◽

Iman S Gurung ◽

Arnold E Pfahnl ◽

Lijuan L Shang ◽

Shahriar Iravanian ◽

...

Keyword(s):

Mouse Model ◽

Brugada Syndrome ◽

Fluorescent Microscopy ◽

Gene Mutations ◽

Oxidase Inhibitor ◽

Pyridine Nucleotides ◽

Programmed Electrical Stimulation ◽

Amino Acid Homology ◽

Cardiac Sodium Channel ◽

Glycerol 3 Phosphate Dehydrogenase

Recently, glycerol-3-phosphate dehydrogenase 1-like (GPD1-L) gene mutations have been shown to reduce cardiac Na + current and cause Brugada Syndrome (BrS). The glycerol-3-phosphate dehydrogenase (GPD) family of genes is involved in nicotinamide adenine dinucleotides (NAD)-dependent energy metabolism, and GDP1-L has >80% amino acid homology with GPD. Therefore, we tested whether mutations in GPD1-L could be acting through NAD (H) to alter Na + current. Human embryonic kidney (HEK) cells stably expressing the human cardiac sodium channel (SCN5A) were used to assess the effects of wild-type (WT) and mutant (MT) GPD1-L on cellular NAD(H) and the effects of NAD(H) on Na + current. A mouse model of BrS was used to assess the effect of reduced NAD + on arrhythmic risk. MT GPD1-L raised cellular NADH level by 4.3 fold (p<0.01) and reduced Na + current by 69.9% (p<0.01). Extracellular NADH (300 μM) raised cellular NADH by 5.3 fold and decreased whole cell peak conductance by 71.4% (p<0.001). Extracellular NAD + (300 μM) raised conductance by 30.3% (p< 0.001). Fluorescent microscopy showed parallel changes in membrane-associated, GFP-tagged Na + channels. Intracellular application of NADH or NAD + resulted in an immediate change in Na + current of −55.5% (p < 0.01) and +66.6% (p < 0.01), respectively. External NAD + could prevent the reduction in Na + current caused by MT GPD1-L. Apocynin (100 μM), an NAD(P)H oxidase inhibitor, or the reducing agent, dithiothreitol (DTT), prevented the NADH-induced reduction in Na + current (p < 0.01). Application of 100 μM NAD + to a mouse model of BrS reduced the programmed electrical stimulation induced ventricular tachycardia. GPD1-L mutations may cause BrS through alterations in cellular NAD(H), and NAD + might represent a novel treatment for BrS.

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