Genetic Variants Associated With Unexplained Sudden Cardiac Death in Adult White and African American Individuals

2021 ◽  
Author(s):  
Liang Guo ◽  
Sho Torii ◽  
Raquel Fernandez ◽  
Ryan E. Braumann ◽  
Daniela T. Fuller ◽  
...  
Keyword(s):  
African American ◽  
Sudden Cardiac Death ◽  
Genetic Variants ◽  
Cardiac Death

P1392Next generation sequencing in lone atrial fibrillation patients

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
I Rudaka ◽  
D Rots ◽  
O Kalejs ◽  
L Gailite
Keyword(s):  
Atrial Fibrillation ◽  
Sudden Cardiac Death ◽  
Genetic Variants ◽  
Cardiac Death ◽  
Structural Heart Disease ◽  
Missense Variant ◽  
Lone Atrial Fibrillation ◽  
Excessive Alcohol Consumption ◽  
Pathogenic Variants ◽  
Rare Genetic Variants

Abstract Background. Minor part of atrial fibrillation (AF) patients develops the disease without any well-known risk factors, which is a particular form of the disease, known as a lone AF. Rare genetic variants were described as causative for lone AF. The aim of this study was to investigate occurrence of rare genetic variants in lone AF patients. Material and Methods. We performed Mendeliome sequencing for 21 lone AF patients. Lone AF was defined as AF in individuals younger than 65 years in the absence of cardiovascular or structural heart disease, endocrinologic or pulmonary disease, chronic kidney disease, obesity and excessive alcohol consumption. Data analysis was performed by current laboratory pipeline. We analyzed 453 cardiomyopathy, arrhythmias and sudden cardiac death related genes. Results. In eight out of 21 (38%) lone AF patients rare likely pathogenic variants were found (Table 1.). Seven rare truncating TTN variants and one LMNA missense variant were observed. Four unrelated patients were positive for the same TTN variant c.13696 C > T; p.(Gln4566Ter). The same variant was previously found in ARVC patient in our laboratory. Segregation analysis and phenotyping of relatives is ongoing. Conclusions. Rare genetic variants are common causes of the lone atrial fibrillation. TTN gene variant c.13696C > T; p.(Gln4566Ter) is a potential founder variant in the Baltic population. Table 1. Genetic variants in lone AF Gender Age of AF onset Genetic variant Family history Male 53 LMNA: p.(Ser326Thr) AF in mother Male 11 TTN: p.(Trp31854Ter) AF in father Male 30 TTN: p.(GLn4566Ter) AF in uncle Female 45 TTN: p.(GLn4566Ter) Negative Male 37 TTN: p.(GLn4566Ter) AF in father Male 25 TTN: p.(GLn4566Ter) AF in father, maternal and paternal grandmother Female 60 TTN: p.(Arg27414Ter) Sudden cardiac death at the age of 50 in grand father Female 52 TTN: p.(Arg1012Ter) AF in mother

scholarly journals Common Genetic Variants Associated with Sudden Cardiac Death: The FinSCDgen Study

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e41675 ◽  
Author(s):  
Annukka M. Lahtinen ◽  
Peter A. Noseworthy ◽  
Aki S. Havulinna ◽  
Antti Jula ◽  
Pekka J. Karhunen ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Genetic Variants ◽  
Cardiac Death ◽  
Common Genetic Variants

scholarly journals β2-Adrenergic Receptor Genetic Variants and Risk of Sudden Cardiac Death

Circulation ◽  
2006 ◽  
Vol 113 (15) ◽  
pp. 1842-1848 ◽  
Author(s):  
Nona Sotoodehnia ◽  
David S. Siscovick ◽  
Matteo Vatta ◽  
Bruce M. Psaty ◽  
Russell P. Tracy ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Genetic Variants ◽  
Adrenergic Receptor ◽  
Cardiac Death ◽  
Β2 Adrenergic Receptor

scholarly journals Cumulative effects of common genetic variants on risk of sudden cardiac death

2015 ◽  
Vol 7 ◽  
pp. 88-91 ◽  
Author(s):  
Adriana Huertas-Vazquez ◽  
Christopher P. Nelson ◽  
Janet S. Sinsheimer ◽  
Kyndaron Reinier ◽  
Audrey Uy-Evanado ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Genetic Variants ◽  
Cardiac Death ◽  
Cumulative Effects ◽  
Common Genetic Variants

scholarly journals Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death

2017 ◽  
Vol 38 (6) ◽  
pp. 1262-1268 ◽  
Author(s):  
Eva Fernlund ◽  
A. Wålinder Österberg ◽  
E. Kuchinskaya ◽  
M. Gustafsson ◽  
K. Jansson ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Dilated Cardiomyopathy ◽  
Genetic Variants ◽  
Cardiac Death ◽  
Swedish Family ◽  
History Of

scholarly journals Genetic contributions to the expression of acquired causes of cardiac hypertrophy in non-ischemic sudden cardiac death victims

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lauri Holmström ◽  
Katri Pylkäs ◽  
Anna Tervasmäki ◽  
Juha Vähätalo ◽  
Katja Porvari ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Genetic Variants ◽  
Cardiac Death ◽  
Heart Weight ◽  
Gene Variants ◽  
Myocardial Disease ◽  
Myocardial Diseases ◽  
Pathogenic Variants ◽  
Uncertain Significance ◽  
Genetic Contributions

AbstractThe contribution of genetic variants to non-ischemic sudden cardiac death (SCD) due to acquired myocardial diseases is unclear. We studied whether SCD victims with hypertension/obesity related hypertrophic myocardial disease harbor potentially disease associated gene variants. The Fingesture study has collected data from 5869 autopsy-verified SCD victims in Northern Finland. Among SCD victims, 740 (13%) had hypertension and/or obesity as the most likely explanation for myocardial disease with hypertrophy and fibrosis. We performed next generation sequencing using a panel of 174 cardiac genes for 151 such victims with the best quality of DNA. We used 48 patients with hypertension and hypertrophic heart as controls. Likely pathogenic variants were identified in 15 SCD victims (10%) and variants of uncertain significance (VUS) were observed in additional 43 SCD victims (28%). In controls, likely pathogenic variants were present in two subjects (4%; p = 0.21) and VUSs in 12 subjects (25%; p = 0.64). Among SCD victims, presence of potentially disease-related variants was associated with lower mean BMI and heart weight. Potentially disease related gene variants are common in non-ischemic SCD but further studies are required to determine specific contribution of rare genetic variants to the extent of acquired myocardial diseases leading to SCD.

Broad-based molecular autopsy: a potential tool to investigate the involvement of subtle cardiac conditions in sudden unexpected death in infancy and early childhood

2015 ◽  
Vol 100 (10) ◽  
pp. 952-956 ◽  
Author(s):  
Montserrat Santori ◽  
Alejandro Blanco-Verea ◽  
Rocio Gil ◽  
Judith Cortis ◽  
Katrin Becker ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Genetic Variants ◽  
Early Onset ◽  
Cardiac Death ◽  
Sudden Unexpected Death ◽  
Unexpected Death ◽  
Molecular Autopsy ◽  
Sudden Unexplained Death ◽  
Unexplained Death ◽  
In Infants And Children

ObjectivesSudden unexplained death in children is a tragic and traumatic event, often worsened when the cause of death cannot be determined. This work aimed to investigate the presence of putative pathogenic genetic variants in a broad spectrum of cardiomyopathy, channelopathy and aortic disease associated genes that may have increased these children's vulnerability to sudden cardiac death.DesignWe performed molecular autopsy of 41 cases of sudden unexplained death in infants and children through massive parallel sequencing of up to 86 sudden cardiac death-related genes. Multiple in silico analyses were conducted together with a thorough review of the literature in order to prioritise the putative pathogenic variants.ResultsA total of 63 variants in 35 cases were validated. The largest proportion of these variants is located within cardiomyopathy genes although this would have been more expected of channelopathy gene variants. Subtle microscopic features of heart tissue may indicate the presence of an early onset cardiomyopathy as a predisposing condition to sudden unexpected death in some individuals.ConclusionsNext-generation sequencing technologies reveal the existence of a wide spectrum of rare and novel genetic variants in sarcomere genes, compared with that of cardiac ion channels, in sudden unexplained death in infants and children. Our findings encourage further investigation of the role of early onset inherited cardiomyopathies and other diseases involving myocardial dysfunction in these deaths. Early detection of variants in these individuals could help to unmask subtle forms of disease within their relatives, who would eventually benefit from better counselling about their genetic history.

scholarly journals Genetics of Unexplained Sudden Cardiac Death in Adult Caucasian and African American Individuals Living in the State of Maryland

2019 ◽  
Author(s):  
Liang Guo ◽  
Sho Torii ◽  
Raquel Fernandez ◽  
Ryan E. Braumann ◽  
Ka Hyun Paek ◽  
...  
Keyword(s):  
African Americans ◽  
Sudden Cardiac Death ◽  
Genetic Variants ◽  
Cardiac Death ◽  
Pathological Finding ◽  
Arrhythmogenic Right Ventricular Dysplasia ◽  
The United States ◽  
The State ◽  
Pathological Examination ◽  
Medical Examiner

ABSTRACTBackgroundUnexplained-sudden cardiac death (SCD) describes SCD with no cause identified after a comprehensive autopsy and toxicologic examination. Genetic testing helps to diagnose inherited cardiac diseases in unexplained-SCD, however, the relationship between pathogenic or likely pathogenic (P/LP) variants of inherited cardiomyopathies and primary electrical disorders (PED) and risk of unexplained-SCD in adults living the United States has never been systematically examined.MethodsWe performed sequencing of 29 cardiomyopathy and 39 arrhythmia genes in 413 African-Americans and Caucasians (≥18 years-old) who died of unexplained-SCD (median age; 41 years-old, 37% females, 50% African-Americans) and whose hearts were found to have no gross pathological finding upon referral to our institution for pathologic consultation from the State of Maryland Medical Examiner. We examined P/LP variants in these genes to study the association between presence of these variants and unexplained-SCD.Results143/413 (34.6%) subjects had variants considered P/LP for cardiomyopathy and/or PED (i.e. Brugada Syndrome (BrS), long QT syndrome (LQTS), and arrhythmogenic right ventricular dysplasia (ARVD)). In total, 102 (24.7%) subjects harbored 86 P/LP variants for cardiomyopathies and 60 (14.5%) subjects carried 76 P/LP variants for PED. The following pathogenic variants were identified: 68 P/LP variants for hypertrophic cardiomyopathy (HCM) in 79/413 (19.1%) subjects, 18 P/LP variants for dilated cardiomyopathy (DCM) in 22/413 subjects (5.3%), and 76 P/LP variants in 60/413 (14.5%) for PED. There were greater than 121.0- and 138.5-fold median enrichments (431.4- and 200.0-fold cumulative enrichments) in these cardiomyopathy and arrhythmia variants in victims of unexplained SCD versus the general population, respectively. Among these P/LP positive carriers, combinations of conditions were found, including 14/413 (2.4%) having both HCM and PED variants, and 5/413 (1.2%) with DCM and PED variants. African Americans (AA) and Caucasians were equally likely to harbor P/LP variants (32.7% versus 36.6%, p=0.5), but AA had a higher frequent variants of unknown significance.ConclusionsThis study represents the largest examination reported on the association between cardiomyopathy and arrhythmia P/LP genetic variants and unexplained-SCD in adults with no gross abnormality on rigorous pathological examination. Nearly one-third of those with unexplained-SCD were carriers of P/LP variants. Our findings with respect to both the association of unexplained SCD with cardiomyopathy genes and race-specific genetic variants suggest new avenues of study for this poorly understood entity.

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