Analysis of SCN5A Gene Variants in East Slovak Patients with Cardiomyopathy

Priganc, Mariana; Zigová, Michaela; Boroňová, Iveta; Bernasovská, Jarmila; Dojčáková, Dana; Szabadosová, Viktória; Blaščáková, Marta Mydlárová; Tóthová, Iveta; Kmeč, Ján; Bernasovský, Ivan

doi:10.1002/jcla.22037

Cited by 7 publications

(4 citation statements)

References 26 publications

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“…The specific variant has been reported before and is associated with arrhythmogenic right ventricular cardiomyopathy. A study of three exons of SCN5A in a cohort of dilated and hypertrophic cardiomyopathy patients and controls identified many missense genetic variants classified as potentially damaging and disease-causing [23]. Both parents of the second patient were healthy and showed no clinical features associated with HMC.…”

Section: Resultsmentioning

confidence: 99%

Double heterozygosity of novel variants found in patients with severe clinical phenotype of cardiovascular disorders

Josifovska

Vazharova

Balabanski³

et al. 2018

Biotechnology & Biotechnological Equipment

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Cardiovascular diseases (CVD) comprise a broad range of disorders of the heart and blood vessels. In this study, we used next-generation sequencing with a panel that includes 174 genes connected to CVD in order to investigate the possible genetic causes that underline some clinical phenotypes and their severity. Two patients were found with double heterozygosity, each carrying one new variant. One patient with supravalvular aortic stenosis has novel ELN: c.890-1G>A and a known variant SCN5A: p.Gly9Val in a heterozygous state, whereas another patient with hypertrophic cardiomyopathy has a heterozygous novel CACNA1C: p.Arg514Gly and a known SCN5A: p. Arg800His variant. This method proved to be useful in determining the mutation status in correlation with the severity of the clinical phenotype and can further clarify cases where the clinical status could not be explained only by single gene mutation detected by standard methods.

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Section: Resultsmentioning

confidence: 99%

Double heterozygosity of novel variants found in patients with severe clinical phenotype of cardiovascular disorders

Josifovska

Vazharova

Balabanski³

et al. 2018

Biotechnology & Biotechnological Equipment

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“…Анализируя литературные источники, мы отметили исследования, которые позволяют делать выводы о том, что нарушение работы в структуре гена SCN5A в разных вариантах может способствовать развитию ДКМП [6][7][8][9][10][11][12].…”

Section: материал и методыunclassified

“…Скрининг мутаций трех выбранных экзонов гена SCN5A в группе из 27 пациентов с ДКМП, 12 пациентов с гипертрофической кардиомиопатией и 16 человек контрольной группы выявил 10 миссенс-генетических вариантов. Три из них (T1247I, A1260D и G1262S), все в экзоне 21 гена SCN5A, были вариантами, потенциально повреждающими и вызывающими болезнь [12].…”

Section: материал и методыunclassified

Association of SCN5A gene polymorphism with dilated cardiomyopathy

Nikulina

Kuznetsova

Чернова

et al. 2021

Racionalʹnaâ farmakoterapiâ v kardiologii

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Subjects and methods. The study included patients with IDC (group 1; n=111, 89.2% men, average age 51.7±9.7 years) and ICM (group 2; n=110, 91.5% men, average age 58.7±8.4 years). All patients (IDC and ICM) underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the group 1. And those patients who were reliably diagnosed with coronary artery disease were in the group 2, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. The control group (n=121, average age 53.6±4.8 years) included patients who had no manifestations of cardiovascular diseases. The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the A/G polymorphism of the SCN5A gene (rs1805124).Results. In the group with IDC 51.4% of patients were carriers of the common homozygous AA genotype, the heterozygous AG genotype-40.5%, and the rare homozygous GG genotype-8.1%. In the control group 63.3% of patients were identified as carriers of a homozygous genotype by a common allele, and 33.5% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 3.2%. The analysis revealed a statistically significant decrease in the frequency of carrying the homozygous AA genotype in patients with IDC compared to the control group of the rs1805124 polymorphism of the SCN5A gene. In the group of patients with ICM, the А allele (69.5% vs. 80.1%, p=0.003) and the AA genotype (50.9% vs. 63.3%, p=0.030) were significantly less common than in the control group. The rare homozygous GG genotype was statically more common in patients with ICM compared to the control group (11.8% vs. 3.2%, p=0.004). Also, the G allele in the group of patients with ICM was detected statically significantly more often than in the control group (30.5% vs. 19.9%, p= 0.003).Conclusion. The polymorphic locus rs1805124 of the SCN5A gene is associated with both IDC and ICM. Homozygous genotype AA and allele A are conditionally protective factors for the development of these conditions in men.

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“…The majority of patients (80.8 %) had severe left ventricular systolic dysfunction with ejection fraction < 30 %; 1.8 % of patients had preserved left ventricular ejection fraction ≥ 50 % (8). Despite of the number of CM patients and the availability of NGS methods, the current diagnostic tests in Slovakia are still based on Sanger sequencing of a few genes (9).…”

Section: Introductionmentioning

confidence: 99%

Targeted next-generation sequencing in Slovak cardiomyopathy patients

Nagyová¹,

Radvánszky²,

Hýblová³

et al. 2019

BLL

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OBJECTIVES: For the fi rst time we used targeted next-generation sequencing to detect candidate pathogenic variants in Slovak cardiomyopathy patients. BACKGROUND: Targeted next-generation sequencing is considered to be the best practice in genetic diagnostics of cardiomyopathies. However, in Slovakia, with high cardiomyopathies prevalence of 1/440, the current diagnostic tests are still based on Sanger sequencing of a few genes. Consequently, little is known about the exact contribution of pathogenic variants in known cardiomyopathy genes in Slovak patients. METHODS: We used a panel of 46 known cardiomyopathy-associated genes to detect genetic variants in 16 Slovak cardiomyopathy patients (6 dilated, 8 hypertrophic, 2 non-compaction subtypes). RESULTS: We identifi ed candidate pathogenic variants in 11 of 16 patients (69 %). Genes with higher count of candidate pathogenic variants were MYBPC3, MYH and TTN, each with 3 different variants. Seven variants ACTC1 (c.329C>T), ANKRD1 (c.683G>T), MYH7 (c.1025C>T), PKP2 (c.2003delA), TTN (c.51655C>T, c.84841G>T, c.101874_101881delAGAATTTG) have been detected for the fi rst time and might represent Slovak-specifi c genetic cause. CONCLUSIONS: We have performed genetic testing of previously untested Slovak cardiomyopathy patients using next-generation sequencing cardiomyopathy gene panel. Given the high percentage of candidate pathogenic variants it should be recommended to implement this method into routine genetic diagnostic practice in Slovakia (Tab. 4, Ref. 39).

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Analysis of SCN5A Gene Variants in East Slovak Patients with Cardiomyopathy

Abstract: Data from this study demonstrate that SCN5A gene variants have important role in the etiopathogenesis of dilated and HCM.

Cited by 7 publications

References 26 publications

Double heterozygosity of novel variants found in patients with severe clinical phenotype of cardiovascular disorders

Double heterozygosity of novel variants found in patients with severe clinical phenotype of cardiovascular disorders

Association of SCN5A gene polymorphism with dilated cardiomyopathy

Targeted next-generation sequencing in Slovak cardiomyopathy patients

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