Clemens, D;
Gray, B;
Bagnall, R;
Tester, D;
Dotzler, S;
Giudicessi, J;
Matthews, E;
... Ackerman, M; + view all
(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.
Circulation: Genomic and Precision Medicine
, 13
(2)
10.1161/CIRCGEN.119.002731.
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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.
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