Genetic aspects and investigation of sudden death in young people

Lambiase, Pier D.; Elliott, Perry

doi:10.7861/clinmedicine.8-6-607

Cited by 4 publications

(4 citation statements)

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“…A genetic workup in these cases might confirm or reveal inherited cardiac diseases such as Long QT syndrome and Brugada syndrome where sudden cardiac death may be the initial symptom and thereby help to identify patients at risk in the family [15,22]. …”

Section: Discussionmentioning

confidence: 99%

“…In the clinical setting wgaDNA from DBS samples can become very important for instance in cases of otherwise unexplained deaths where material suitable for DNA testing is otherwise not retrievable. A genetic workup in these cases might confirm or reveal inherited cardiac diseases such as Long QT syndrome and Brugada syndrome where sudden cardiac death may be the initial symptom and thereby help to identify patients at risk in the family [ 15 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

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Whole-genome amplified DNA from stored dried blood spots is reliable in high resolution melting curve and sequencing analysis

et al. 2011

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BackgroundThe use of dried blood spots (DBS) samples in genomic workup has been limited by the relative low amounts of genomic DNA (gDNA) they contain. It remains to be proven that whole genome amplified DNA (wgaDNA) from stored DBS samples, constitutes a reliable alternative to gDNA.We wanted to compare melting curves and sequencing results from wgaDNA derived from DBS samples with gDNA derived from whole blood.MethodsgDNA was extracted from whole blood obtained from 10 patients with lone atrial fibrillation (mean age 22.3 years). From their newborn DBS samples, stored at -24°C, genomic DNA was extracted and whole-genome amplified in triplicates. Using high resolution melting curve analysis and direct sequencing in both wgaDNA and gDNA samples, all coding regions and adjacent intron regions of the genes SCN5A and KCNA5 were investigated.ResultsAltered melting curves was present in 85 of wgaDNA samples and 81 of gDNA samples. Sequence analysis identified a total of 31 variants in the 10 wgaDNA samples. The same 31 variants were found in the exact same pattern of samples in the gDNA group. There was no false positive or negative sequence variation in the wgaDNA group.ConclusionsThe use of DNA amplified in triplicates from DBS samples is reliable and can be used both for high resolution curve melting analysis as well as direct sequence analysis. DBS samples therefore can serve as an alternative to whole blood in sequence analysis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Whole-genome amplified DNA from stored dried blood spots is reliable in high resolution melting curve and sequencing analysis

et al. 2011

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“…Cardiomyopathies are estimated to be responsible for 10–35% of sudden cardiac deaths (SCDs) in the young population [ 8 , 9 , 10 ]. Other possible complications of cardiomyopathies include heart failure, stroke and thromboembolic complications.…”

Section: Introductionmentioning

confidence: 99%

“…Other possible complications of cardiomyopathies include heart failure, stroke and thromboembolic complications. Because cardiac expression of inherited cardiomyopathies is frequently delayed, the disease is often clinically silent for a number of years and complications such as SCD can be the presenting feature [ 4 , 9 , 10 , 11 ]. Molecular genetic testing may be performed after cardiac death, especially after SCD and autopsy, and the guidelines promote the prescription of post-mortem genetic testing with a relatively high level of recommendation in the context of SCD and suspected channelopathy or cardiomyopathy [ 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical impact of post-mortem genetic testing in cardiac death and cardiomyopathy

et al. 2020

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AbstractPost-mortem genetic analyses may help to elucidate the cause of cardiac death. The added value is however unclear when a cardiac disease is already suspected or affirmed. Our aim was to study the feasibility and medical impact of post-mortem genetic analyses in suspected cardiomyopathy. We studied 35 patients with cardiac death and suspected cardiomyopathy based on autopsy or clinical data. After targeted sequencing, we identified 15 causal variants in 15 patients (yield 43%) in sarcomeric (n = 8), desmosomal (n = 3), lamin A/C (n = 3) and transthyretin (n = 1) genes. The results had various impacts on families, i.e. allowed predictive genetic testing in relatives (15 families), planned early therapeutics based on the specific underlying gene (5 families), rectified the suspected cardiomyopathy subtype (2 families), assessed the genetic origin of cardiomyopathy that usually has an acquired cause (1 family), assessed the diagnosis in a patient with uncertain borderline cardiomyopathy (1 family), reassured the siblings because of a de novo mutation (2 families) and allowed prenatal testing (1 family). Our findings suggest that post-mortem molecular testing should be included in the strategy of family care after cardiac death and suspected cardiomyopathy, since genetic findings provide additional information useful for relatives, which are beyond conventional autopsy.

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