Molecular autopsy in sudden cardiac death – ethical issues and clinical implication for relatives

Micheu, Miruna Mihaela; Popescu, Ionut Radu; Capatana, Corneliu Octavian; Bărbării, Ligia Elena; Dorobanțu, Maria

doi:10.4323/rjlm.2016.157

Cited by 2 publications

(2 citation statements)

References 71 publications

(78 reference statements)

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“…Importantly, sudden cardiac death is frequently the first expression of the disease. Understanding the underlying genetic cause is the centerpiece of a timely diagnosis and targeted treatment[ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Patient-specific induced pluripotent stem cells as “disease-in-a-dish” models for inherited cardiomyopathies and channelopathies – 15 years of research

Micheu¹,

Rosca²

2021

WJSC

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Among inherited cardiac conditions, a special place is kept by cardiomyopathies (CMPs) and channelopathies (CNPs), which pose a substantial healthcare burden due to the complexity of the therapeutic management and cause early mortality. Like other inherited cardiac conditions, genetic CMPs and CNPs exhibit incomplete penetrance and variable expressivity even within carriers of the same pathogenic deoxyribonucleic acid variant, challenging our understanding of the underlying pathogenic mechanisms. Until recently, the lack of accurate physiological preclinical models hindered the investigation of fundamental cellular and molecular mechanisms. The advent of induced pluripotent stem cell (iPSC) technology, along with advances in gene editing, offered unprecedented opportunities to explore hereditary CMPs and CNPs. Hallmark features of iPSCs include the ability to differentiate into unlimited numbers of cells from any of the three germ layers, genetic identity with the subject from whom they were derived, and ease of gene editing, all of which were used to generate “disease-in-a-dish” models of monogenic cardiac conditions. Functionally, iPSC-derived cardiomyocytes that faithfully recapitulate the patient-specific phenotype, allowed the study of disease mechanisms in an individual-/allele-specific manner, as well as the customization of therapeutic regimen. This review provides a synopsis of the most important iPSC-based models of CMPs and CNPs and the potential use for modeling disease mechanisms, personalized therapy and deoxyribonucleic acid variant functional annotation.

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Section: Introductionmentioning

confidence: 99%

Patient-specific induced pluripotent stem cells as “disease-in-a-dish” models for inherited cardiomyopathies and channelopathies – 15 years of research

Micheu¹,

Rosca²

2021

WJSC

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“…Pediatric CMPs and CNPs, although rare, represent a serious condition, remaining a leading cause of death in children. In previously healthy children, conventional autopsy of adolescents with SCD fails to establish the diagnosis in the absence of genetic analysis [ 2 ], as certain CMPs and CNPs do not display structural abnormalities. For better management for these patients, etiology-specific treatment is needed, based mainly on a comprehensive evaluation, including genetic analysis, as this increases the accuracy of the etiological diagnosis, with consequences for treatment, evolution and family genetic counselling.…”

Section: Introductionmentioning

confidence: 99%

The Multifaced Perspectives of Genetic Testing in Pediatric Cardiomyopathies and Channelopathies

Popa-Fotea

Cojocaru

Scafa-Udriște

et al. 2020

JCM

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Pediatric inherited cardiomyopathies (CMPs) and channelopathies (CNPs) remain important causes of death in this population, therefore, there is a need for prompt diagnosis and tailored treatment. Conventional evaluation fails to establish the diagnosis of pediatric CMPs and CNPs in a significant proportion, prompting further, more complex testing to make a diagnosis that could influence the implementation of lifesaving strategies. Genetic testing in CMPs and CNPs may help unveil the underlying cause, but needs to be carried out with caution given the lack of uniform recommendations in guidelines about the precise time to start the genetic evaluation or the type of targeted testing or whole-genome sequencing. A very diverse etiology and the scarce number of randomized studies of pediatric CMPs and CNPs make genetic testing of these maladies far more particular than their adult counterpart. The genetic diagnosis is even more puzzling if the psychological impact point of view is taken into account. This review aims to put together different perspectives, state-of-the art recommendations—synthetizing the major indications from European and American guidelines—and psychosocial outlooks to construct a comprehensive genetic assessment of pediatric CMPs and CNPs.

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Molecular autopsy in sudden cardiac death – ethical issues and clinical implication for relatives

Cited by 2 publications

References 71 publications

Patient-specific induced pluripotent stem cells as “disease-in-a-dish” models for inherited cardiomyopathies and channelopathies – 15 years of research

Patient-specific induced pluripotent stem cells as “disease-in-a-dish” models for inherited cardiomyopathies and channelopathies – 15 years of research

The Multifaced Perspectives of Genetic Testing in Pediatric Cardiomyopathies and Channelopathies

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