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Triadin Knockout Syndrome Is Absent in a Multi-Center Molecular Autopsy Cohort of Sudden Infant Death Syndrome and Sudden Unexplained Death in the Young and Is Extremely Rare in the General Population

Clemens, DJ; Gray, B; Bagnall, RD; Tester, DJ; Dotzler, SM; Giudicessi, JR; Matthews, E; Semsarian, C; Behr, ER; Ackerman, MJ (2020) Triadin Knockout Syndrome Is Absent in a Multi-Center Molecular Autopsy Cohort of Sudden Infant Death Syndrome and Sudden Unexplained Death in the Young and Is Extremely Rare in the General Population. Circ Genom Precis Med, 13 (2). e002731. ISSN 2574-8300 https://doi.org/10.1161/CIRCGEN.119.002731
SGUL Authors: Behr, Elijah Raphael

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Abstract

Background: Triadin knockout syndrome (TKOS) is a potentially lethal arrhythmia disorder caused by recessively inherited null variants in TRDN-encoded cardiac triadin. Despite its malignant phenotype, the prevalence of TKOS in sudden infant death syndrome and sudden unexplained death in the young is unknown. Methods: Exome sequencing was performed on 599 sudden infant death syndrome and 258 sudden unexplained death in the young cases. Allele frequencies of all TRDN null variants identified in the cardiac-specific isoform of TRDN in the Genome Aggregation Database were used to determine the estimated prevalence and ethnic distribution of TKOS. Results: No triadin null individuals were identified in 599 sudden infant death syndrome and 258 sudden unexplained death in the young exomes. Using the Genome Aggregation Database, we estimate the overall prevalence of TKOS to be ≈1:22.7 million individuals. However, TKOS prevalence is 5.5-fold higher in those of African descent (≈1:4.1 million). Conclusions: TKOS is an exceedingly rare clinical entity that does not contribute meaningfully to either sudden infant death syndrome or sudden unexplained death in the young. However, despite its rarity and absence in large sudden death cohorts, TKOS remains a malignant and potentially lethal disorder which requires further research to better care for these patients.

Item Type: Article
Additional Information: This is a non-final version of an article published in final form in lemens, DJ; Gray, B; Bagnall, RD; Tester, DJ; Dotzler, SM; Giudicessi, JR; Matthews, E; Semsarian, C; Behr, ER; Ackerman, MJ (2020) Triadin Knockout Syndrome is Absent in a Multi-Center Molecular Autopsy Cohort of Sudden Infant Death Syndrome and Sudden Unexplained Death in the Young and is Extremely Rare in the General Population. Circ Genom Precis Med.
Keywords: Triadin
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Circ Genom Precis Med
ISSN: 2574-8300
Language: eng
Dates:
DateEvent
April 2020Published
13 March 2020Published Online
25 February 2020Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
1154992National Health and Medical Research Councilhttp://dx.doi.org/10.13039/501100000925
1122330National Health and Medical Research Councilhttp://dx.doi.org/10.13039/501100000925
PubMed ID: 32167373
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/111786
Publisher's version: https://doi.org/10.1161/CIRCGEN.119.002731

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