Expression and Intracellular Localization of an
            <b>
              <i>SCN5A</i>
            </b>
            Double Mutant R1232W/T1620M Implicated in Brugada Syndrome

Baroudi, Ghayath; Acharfi, Said; Larouche, Chantal; Chahine, Mohamed

doi:10.1161/hh0102.102977

Cited by 141 publications

(76 citation statements)

References 33 publications

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“…30,31) Therefore, it remains controversial as to whether this variant is sufficient to cause BrS. c.4437 + 5 g>a identified in patient B16 has previously been reported as a BrS-causing mutation in the absence of functional analysis.…”

Section: Discussionmentioning

confidence: 99%

Identification of Six Novel SCN5A Mutations in Japanese Patients With Brugada Syndrome

et al. 2011

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SummaryMutations in SCN5A are linked to Brugada syndrome in approximately 20% of all cases (BrS1). Several dozen distinct SCN5A mutations in BrS1 have been associated with the increased risk of cardiac arrhythmias. However, the genotype-phenotype relationship remains elusive. The current study analyzed the SCN5A gene to elucidate the potential variability of clinical features in Japanese BrS1 subjects. Subjects of the present study included 30 probands (25 male subjects, 45 ± 15 years of age) with Brugada-pattern ECG. Seven patients had been resuscitated from cardiopulmonary arrest (CPA group). Another 10 patients had a history of syncope (Sy group), and 13 more remain asymptomatic (Asy group). We identified 8 different SCN5A mutations, including 6 novel mutations (CPA group: 1/7, Sy group: 3/10, Asy group: 4/13). An A735E mutation (located at segment (S)1 in domain (D)2) was identified in the CPA group. A novel splice acceptor site mutation (c.393-1c>t), which may produce a prematurely truncated protein, was identified in the Sy group. An E1784K mutation (C-terminus) and a novel mutation V1951M (C-terminus) were also identified in the Sy group. Four novel missense mutations, A586T (D1-D2 linker), R689H (D1-D2 linker), S1553R (S1-S2 in D4), and Q1706H (S5-Pore in D4) were identified in the Asy group. These data may help us understand the genetic heterogeneity of BrS1, which is more prevalent in Japanese than in whites and other ethnic groups. (Int Heart J 2011; 52: 27-31) Key words: Brugada syndrome, SCN5A, Mutation T he Brugada syndrome (BrS), characterized by ST-segment elevations in the right precordial ECG leads without structural heart disease, is a hereditable disease associated with an increased risk of sudden death due to polymorphic ventricular tachycardia or ventricular fibrillation (VF).1) Genetic analyses of BrS revealed that BrS is genetically heterogeneous, and is linked to at least 7 different genes. [2][3][4][5][6][7][8] Mutations in SCN5A, which encodes the pore-forming subunit of the cardiac voltage-gated sodium channel, have been associated with the major form of BrS (BrS1) in approximately 20% of cases. [9][10][11] The clinical severity of BrS may vary with the responsible genes and/or mutation sites, although the genotypephenotype relationship remains poorly characterized. The presence of SCN5A mutations is not related to the severity of the disease.9,10,12) However, Meregalli, et al have recently reported that the type of SCN5A mutation in BrS1 in European countries may determine the clinical severity.13) Because the clinical features of BrS vary among different ethnicities, 14,15) it is of great value to investigate the genotype-phenotype relationship of BrS in Asians in whom the ratio of BrS patients is relatively high compared to subjects from different ethnic backgrounds.In the present study, we analyzed the SCN5A gene to elucidate the potential variability of clinical features of BrS1 subjects recruited from Gunma University Hospital. Consequently, we identified 8 SCN5A mutations, incl...

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Section: Discussionmentioning

confidence: 99%

Identification of Six Novel SCN5A Mutations in Japanese Patients With Brugada Syndrome

et al. 2011

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“…Many SCN5A mutations have been documented in patients with Brugada syndrome in a number of ethnic groups. While some of the mutations in the SCN5A gene lead to changes in the biophysical characteristics of the sodium channel, i.e., a reduction in the fast sodium channel current, the others are unlikely to cause functional alterations in the channel (Chen et al 1998;Iwasa et al 2000;Baroudi et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of the cardiac sodium channel gene SCN5A in Koreans with Brugada syndrome

Shin¹,

Jang

Park

et al. 2004

J Hum Genet

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The SCN5A gene encodes the alpha subunit of the human cardiac voltage-gated sodium channel. Mutations in SCN5A are responsible for Brugada syndrome, an inherited cardiac disease that leads to idiopathic ventricular fibrillation (IVF) and sudden death. In this study, we screened nine individuals from a single family and 12 sporadic patients who were clinically diagnosed with Brugada syndrome. Using PCR-SSCP, DHPLC, and DNA sequencing analysis, we identified a novel single missense mutation associated with Brugada syndrome in the family and detected a C5607T polymorphism in Korean subjects. A single nucleotide substitution of G to A at nucleotide position 3934 changed the coding sense of exon 21 of the SCN5A from glycine to serine (G1262S) in segment 2 of domain III (DIII-S2). Four individuals in the family carried the identical mutation in the SCN5A gene, but none of the 12 sporadic patients did. This mutation was not found in 150 unrelated normal individuals. This finding is the first report of a novel mutation in SCN5A associated with Brugada syndrome in Koreans.

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“…All these mutations are believed to result in a reduced availability of functional Na v 1.5 channels. This can either be due to a reduced number of channels at the cell membrane (5)(6)(7) or to alterations in its biophysical properties, such as shift in activation and/or inactivation thresholds (7), or acceleration of intermediate inactivation (8). We describe a Danish Brugada syndrome patient with a frame shift deletion mutation in SCN5A giving rise to a truncated protein unable to conduct current.…”

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confidence: 99%

Ventricular tachycardia in a Brugada syndrome patient caused by a novel deletion in SCN5A

Tfelt-Hansen

Jespersen

Hofman-Bang

et al. 2009

Canadian Journal of Cardiology

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Expression and Intracellular Localization of an SCN5A Double Mutant R1232W/T1620M Implicated in Brugada Syndrome

Cited by 141 publications

References 33 publications

Identification of Six Novel SCN5A Mutations in Japanese Patients With Brugada Syndrome

Identification of Six Novel SCN5A Mutations in Japanese Patients With Brugada Syndrome

Genetic analysis of the cardiac sodium channel gene SCN5A in Koreans with Brugada syndrome

Ventricular tachycardia in a Brugada syndrome patient caused by a novel deletion in SCN5A

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