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.

中文翻译：

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Triadin 基因敲除综合征在婴儿猝死综合征和年轻人不明原因猝死的多中心分子尸检队列中不存在，在一般人群中极为罕见。

背景 Triadin 基因敲除综合征 (TKOS) 是一种潜在致命的心律失常疾病，由 TRDN 编码的心脏 triadin 的隐性遗传无效变异引起。尽管具有恶性表型，但 TKOS 在婴儿猝死综合征和年轻人不明原因猝死中的患病率尚不清楚。方法对599例婴儿猝死综合征和258例不明原因猝死的年轻病例进行外显子组测序。基因组聚合数据库中 TRDN 心脏特异性同种型中鉴定的所有 TRDN 无效变体的等位基因频率用于确定 TKOS 的估计患病率和种族分布。结果 599 例婴儿猝死综合征和 258 例年轻外显子组不明原因猝死中未发现 triadin 缺失个体。使用基因组聚合数据库，我们估计 TKOS 的总体患病率约为 1:2270 万人。然而，非洲人后裔的 TKOS 患病率高出 5.5 倍（≈1:410 万）。结论 TKOS 是一种极其罕见的临床疾病，它对婴儿猝死综合征或年轻的不明原因猝死没有任何意义。然而，尽管 TKOS 在大型猝死队列中罕见且不存在，但它仍然是一种恶性且可能致命的疾病，需要进一步研究以更好地照顾这些患者。