The role of genetic testing in unexplained sudden death

Miles, Chris; Behr, Elijah R.

doi:10.1016/j.trsl.2015.06.007

Cited by 37 publications

(35 citation statements)

References 119 publications

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“…In our study, we did not conduct validation testing of biological relatives, but as previous studies have confirmed, such validation testing and examination of family medical histories can help inform interpretation (Bagnall et al 2014;Miles and Behr 2016). For example, findings of a genetic variant in a clearly unaffected relative might signal caution, although because there is variable penetrance with many of these genes, causality would not be ruled out.…”

Section: Discussionmentioning

confidence: 98%

The ethics of conducting molecular autopsies in cases of sudden death in the young

et al. 2016

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Section: Discussionmentioning

confidence: 98%

The ethics of conducting molecular autopsies in cases of sudden death in the young

et al. 2016

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“…Conversely, broad genetic testing in all SCA patients regardless of likelihood of carriership (ie, not only in the case of Sudden Arrhythmogenic Death Syndrome as currently recommended in the guidelines 34 and independent of the underlying phenotype, ie, including MI, DCM, and hypertrophic cardiomyopathy cases) would raise medical, ethical, and logistical concerns. This is particularly true if comprehensive testing of large gene panels is conducted, such as currently used in molecular autopsy, 35 as unavoidably many genetic variants with unclear clinical significance will be discovered in this scenario. A possible compromise could be to systematically test only for the presence of a set of founder mutations with proven pathogenicity in all SCA victims.…”

Section: Discussionmentioning

confidence: 99%

Sudden Cardiac Arrest and Rare Genetic Variants in the Community

Milano

Blom

Lodder

et al. 2016

Circ Cardiovasc Genet

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Background— Sudden cardiac arrest (SCA) ranks among the most common causes of death worldwide. Because SCA is most often lethal, yet mostly occurs in individuals without previously known cardiac disease, the identification of patients at risk for SCA could save many lives. In unselected SCA victims from the community, common genetic variants (which are not disease-causing per se, but may increase susceptibility to ventricular fibrillation) are found to be associated with increased SCA risk. However, whether rare genetic variants contribute to SCA risk in the community is largely unexplored. Methods and Results— We here investigated the involvement of rare genetic variants in SCA risk at the population level by studying the prevalence of 6 founder genetic variants present in the Dutch population (PLN-p.Arg14del, MYBPC3-p.Trp792fsX17, MYBPC3-p.Arg943X, MYBPC3-p.Pro955fsX95, PKP2-p.Arg79X, and the Chr7q36 idiopathic ventricular fibrillation risk haplotype) in a cohort of 1440 unselected Dutch SCA victims included in the Amsterdam Resuscitation Study (ARREST). The six studied founder mutations were found to be more prevalent (1.1%) in the ARREST SCA cohort compared with an ethnically and geographically matched set of controls (0.4%, n=1379; P <0.05) or a set of Dutch individuals drawn from the Genome of the Netherlands (GoNL) study (0%, n=500; P <0.02). Conclusions— This finding provides proof-of-concept for the notion that rare genetic variants contribute to some extent to SCA risk in the community.

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“…The estimated incidence of SCD in the general population in Europe and the United States is between 50 and 100 per 100,000 annually. 1 The vast majority of sudden cardiac deaths are due to ischemic heart disease, hypertensive heart disease, and cerebrovascular disease. Those illnesses are pretty straightforward for forensic pathologists to reveal out, owing to their characteristic anatomical findings, and a review of the relevant history when all other competing causes have been ruled out.…”

Section: Bi̇li̇msel Mektupmentioning

confidence: 99%

Signifificance of Molecular Pathology in Unexplained Sudden Cardiac Deaths: Epigenetics of Cardiomyopathies

Balcıoğlu¹,

Çevik²,

Aşıcıoğlu³

2017

Turkiye Klinikleri J Foren Med

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A AB BS ST TR RA AC CT T Cardiomyopathy, a prominent cause of lethal ventricular arrhythmias and heart failure, may be defined as a primary weakness of the myocardium, impaired myocardial perfusion, or an infiltrative process. Cardiomyopathies are not random in the general population, particularly hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and dilated cardiomyopathy are ought to be kept in mind, occasionally, when investigating sudden deaths of young adults. Cardiomyopathies are associated with multiple genetic and modifiable risk factors; however, given environmental and genetic influences yet to explain precise pathophysiology. Epigenetic mechanisms would endeavour to address some of the gaps in our current knowledge regarding the interaction between nature and nurture in the development of cardiomyopathies.K Ke ey yw wo or rd ds s: : Cardiomyopathies; epigenesis, genetic; death, sudden, cardiac; pathology, molecular; autopsy Ö ÖZ ZE ET T Kalp yetmezliğinin ve ölümcül ventriküler aritminin önemli bir sebebi olan kardiyomiyopati, birinci derecede miyokardiyumun zayıflaması, bozulmuş miyokardiyal perfüzyon ya da bir infiltratif süreç olarak tanımlanabilir. Kardiyomiyopatiler toplumda nadir değildir ve özellikle hipertropik kardiyomiyopati, aritmojenik sağ ventriküler kardiyomiyopati ve dilate kardiyomiyopati varlığı ihtimali, ani genç ölümleri araştırılırken dikkate alınmalıdır. Kardiyomiyopatiler çeşitli genetik ve modifiye edilebilen risk faktörleriyle bağlantılıdır ancak bilinen çevresel ve genetik etkiler patofizyolojiyi tam olarak açıklamada henüz yeterli değildir. Epigenetik mekanizmalar kar diyomiyopatilerin ortaya çıkışındaki kalıtsal ve edinsel unsurların etkileşimini açıklayıcı mevcut bilgilerdeki bazı boşlukların tamamlanmasında umut verici olarak değerlendirilebilir.A An na ah ht ta ar r K Ke el li im me el

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The role of genetic testing in unexplained sudden death

Cited by 37 publications

References 119 publications

The ethics of conducting molecular autopsies in cases of sudden death in the young

The ethics of conducting molecular autopsies in cases of sudden death in the young

Sudden Cardiac Arrest and Rare Genetic Variants in the Community

Signifificance of Molecular Pathology in Unexplained Sudden Cardiac Deaths: Epigenetics of Cardiomyopathies

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