A novel mutation in the SCN5A gene is associated with Brugada syndrome

Life Sciences ◽  
2007 ◽  
Vol 80 (8) ◽  
pp. 716-724 ◽  
Author(s):  
Dong-Jik Shin ◽  
Eunmin Kim ◽  
Sang-Bum Park ◽  
Won-Cheoul Jang ◽  
Yoonsun Bae ◽  
...  
Keyword(s):  
Brugada Syndrome ◽  
Novel Mutation ◽  
Scn5a Gene

scholarly journals Brugada syndrome with a novel missense mutation D252N in SCN5A gene: a case report

2021 ◽  
Vol 63 (7) ◽  
pp. 1-6
Author(s):  
Duy Phuong Dang ◽  
◽  
Minh Ha Nguyen ◽  
Doan Loi Do ◽  
Van Khanh Tran ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Brugada Syndrome ◽  
Autosomal Dominant ◽  
Clinical Symptoms ◽  
Novel Mutation ◽  
Ecg Changes ◽  
Functional Protein ◽  
Conserved Gene ◽  
Scn5a Gene

Brugada syndrome is an inherited cardiac arrhythmia that follows autosomal dominant transmission and can cause sudden death. This paper reported a case of Brugada syndrome in a 43-year-old male patient with no clinical symptoms. Brugada-type 2-ECG changes were accidentally detected. Flecainide test was done and proved positive. Gene analysis revealed a novel missense mutation in the SCN5A gene with a genetic variation of D252N. This novel mutation has not been reported on any genetic databases related to Brugada syndrome. Functional protein analysis software suggested that the mutation occurs in the highly conserved gene and probably has a damaging effect. This is the first Brugada syndrome case reported with a mutation in the SCN5A gene in Vietnam.

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

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.

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

2016 ◽  
Vol 2 (3) ◽  
pp. 261-264 ◽  
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

scholarly journals Compound heterozygous SCN5A gene mutations in asymptomatic Brugada syndrome child

2012 ◽  
Vol 2 (1) ◽  
pp. 11 ◽  
Author(s):  
Elena Sommariva ◽  
Matteo Vatta ◽  
Yutao Xi ◽  
Simone Sala ◽  
Tomohiko Ai ◽  
...  
Keyword(s):  
Brugada Syndrome ◽  
Gene Mutations ◽  
Compound Heterozygous ◽  
Scn5a Gene ◽  
Syndrome Child

scholarly journals Novel heterozygous mutation c.4282G>T in the SCN5A gene in a family with Brugada syndrome

2015 ◽  
Vol 9 (5) ◽  
pp. 1639-1645 ◽  
Author(s):  
JIAN-FANG ZHU ◽  
LI-LI DU ◽  
YUAN TIAN ◽  
YI-MEI DU ◽  
LING ZHANG ◽  
...  
Keyword(s):  
Brugada Syndrome ◽  
Heterozygous Mutation ◽  
Scn5a Gene

scholarly journals De Novo Mutation in the SCN5A Gene Associated with Brugada Syndrome

2015 ◽  
Vol 36 (6) ◽  
pp. 2250-2262 ◽  
Author(s):  
Lumin Wang ◽  
Xiangyun Meng ◽  
Zhiguang Yuchi ◽  
Zhenghang Zhao ◽  
Dehui Xu ◽  
...  
Keyword(s):  
Western Blot ◽  
Brugada Syndrome ◽  
Voltage Dependence ◽  
Confocal Laser Microscopy ◽  
Confocal Laser ◽  
Na Current ◽  
Laser Microscopy ◽  
Window Current ◽  
Scn5a Gene ◽  
Hyperpolarizing Shift

Background: Brugada syndrome (BrS) is a genetically determined cardiac electrical disorder, characterized by typical electrocardiography (ECG) alterations, and it is an arrhythmogenic syndrome that may lead to sudden cardiac death. The most common genotype found among BrS patients is caused by mutations in the SCN5A gene, which lead to a loss of function of the cardiac sodium (Na+) channel (Nav1.5) by different mechanisms. Methods: The assay of confocal laser microscopy and western blot were used to identify the expression and location of L812Q at the cell surface. Characterization of Nav1.5 L812Q mutant Na+ channels was text by patch-clamp recordings, and the PHYRE2 server was used to build a model for human Nav1.5 channel. Results: Here, we report that a novel missense SCN5A mutation, L812Q, localized in the DII-S4 transmembrane region of the Nav1.5 channel protein, was identified in an index patient who showed a typical BrS type-1 ECG phenotype. The mutation was absent in the patient's parents and brother. Heterologous expression of the wild-type (WT) and L812Q mutant Nav1.5 channels in human embryonic kidney cells (HEK293 cells) reveals that the mutation results in a reduction of Na+ current density as well as ∼20 mV hyperpolarizing shift of the voltage dependence of inactivation. The voltage dependence of activation and the time course for recovery from inactivation are not affected by the mutation. The hyperpolarizing shift of the voltage dependence of inactivation caused a reduction of the Na+ window current as well. In addition, western blot and confocal laser microscopy imaging experiments showed that the mutation causes fewer channel to be expressed at the membrane than WT channel. A large proportion of the mutant channels are retained in the cytoplasm, probably in the endoplasmic reticulum. Conclusion: The decrease of channel expression, hyperpolarizing shift of voltage dependence of inactivation, and a decline of Na+ window current caused by L812Q mutation lead to a reduction of Na+ current during the upstroke and the repolarization phases of cardiac action potential, which contribute to the development of BrS.

scholarly journals PNA-Based Graphene Oxide/Porous Silicon Hybrid Biosensor: Towards a Label-Free Optical Assay for Brugada Syndrome

Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2233
Author(s):  
Rosalba Moretta ◽  
Monica Terracciano ◽  
Nicola Borbone ◽  
Giorgia Oliviero ◽  
Chiara Schiattarella ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Porous Silicon ◽  
Brugada Syndrome ◽  
Peptide Nucleic Acid ◽  
Proof Of Concept ◽  
Label Free ◽  
Synthetic Dna ◽  
Cardiac Disorder ◽  
Optical Assay ◽  
Scn5a Gene

Peptide nucleic acid (PNA) is a synthetic DNA mimic that outperforms the properties of traditional oligonucleotides (ONs). On account of its outstanding features, such as remarkable binding affinity towards complementary DNA or RNA as well as high thermal and chemical stability, PNA has been proposed as a valuable alternative to the ON probe in gene-sensor design. In this study, a hybrid transducer made-up of graphene oxide (GO) nano-sheets covalently grafted onto a porous silicon (PSi) matrix has been investigated for the early detection of a genetic cardiac disorder, the Brugada syndrome (BS). A functionalization strategy towards the realization of a potential PNA-based device is described. A PNA, able to detect the SCN5A gene associated with the BS, has been properly synthesized and used as a bioprobe for the realization of a proof-of-concept label-free optical PNA-biosensor. PSi reflectance and GO photoluminescence signals were simultaneously exploited for the monitoring of the device functionalization and response.

scholarly journals A NovelSCN5AMutation in a Patient with Coexistence of Brugada Syndrome Traits and Ischaemic Heart Disease

2009 ◽  
Vol 2009 ◽  
pp. 1-4
Author(s):  
Anders G. Holst ◽  
Kirstine Calloe ◽  
Thomas Jespersen ◽  
Pernille Cedergreen ◽  
Bo G. Winkel ◽  
...  
Keyword(s):  
Heart Disease ◽  
Sudden Cardiac Death ◽  
Ischaemic Heart Disease ◽  
Brugada Syndrome ◽  
Cardiac Death ◽  
Novel Mutation ◽  
Index Patient ◽  
Proarrhythmic Effect ◽  
Electrical Heart Disease ◽  
Disease Entities

Brugada syndrome (BrS) is a primary electrical heart disease, which can lead to sudden cardiac death. In older patients with BrS, the disease may coexist with ischaemic heart disease (IHD) and recent studies support a synergistic proarrhythmic effect of the two disease entities. We report a case that illustrates this. The index patient was a middle-aged patient with BrS traits, IHD, and aborted sudden cardiac death. Mutation analysis discovered a novel mutation P468L in theNaV1.5 sodium channel. Surprisingly, voltage-clamp experiments on the wild-type and mutantNaV1.5 channels expressed in HEK cells revealed no functional effect of the mutation. In a patient like ours, the distinction between IHD and BrS as the cause of an aborted sudden cardiac death is hard to establish and mounting evidence shows that coexistence of the two may have a synergistic proarrhythmic effect.

scholarly journals Structural myocardial abnormalities in asymptomatic family members with Brugada syndrome and SCN5A gene mutation

2009 ◽  
Vol 30 (14) ◽  
pp. 11763-11763 ◽  
Author(s):  
Andrea Frustaci ◽  
Matteo A. Russo ◽  
Cristina Chimenti
Keyword(s):  
Gene Mutation ◽  
Brugada Syndrome ◽  
Family Members ◽  
Scn5a Gene
Sign in / Sign up

Export Citation Format

Share Document