Bard Angela M, Clark Lindsay V, Cosgun Erdal, Aldinger Kimberly A, Timms Andrew, Quina Lely A, Lavista Ferres Juan M, Jardine David, Haas Elisabeth A, Becker Tatiana M, Pagan Chelsea M, Santani Avni, Martinez Diego, Barua Soumitra, McNutt Zakkary, Nesbitt Addie, Mitchell Edwin A, Ramirez Jan-Marino
medRxiv. 2023 Nov 29:2023.09.11.23295207. doi: 10.1101/2023.09.11.23295207.
To gain insights into potential genetic factors contributing to the infant's vulnerability to Sudden Unexpected Infant Death (SUID).
Whole Genome Sequencing (WGS) was performed on 145 infants that succumbed to SUID, and 576 healthy adults. Variants were filtered by gnomAD allele frequencies and predictions of functional consequences.
Variants of interest were identified in 86 genes, 63.4% of our cohort. Seventy-one of these have been previously associated with SIDS/SUID/SUDP. Forty-three can be characterized as cardiac genes and are related to cardiomyopathies, arrhythmias, and other conditions. Variants in 22 genes were associated with neurologic functions. Variants were also found in 13 genes reported to be pathogenic for various systemic disorders. Variants in eight genes are implicated in the response to hypoxia and the regulation of reactive oxygen species (ROS) and have not been previously described in SIDS/SUID/SUDP. Seventy-two infants met the triple risk hypothesis criteria (Figure 1).
Our study confirms and further expands the list of genetic variants associated with SUID. The abundance of genes associated with heart disease and the discovery of variants associated with the redox metabolism have important mechanistic implications for the pathophysiology of SUID.
深入了解导致婴儿易患婴儿不明原因猝死（SUID）的潜在遗传因素。
对145例死于SUID的婴儿和576名健康成年人进行全基因组测序（WGS）。通过gnomAD等位基因频率和功能后果预测对变异进行筛选。
在86个基因中鉴定出感兴趣的变异，占我们队列的63.4%。其中71个基因先前已与婴儿猝死综合征（SIDS）/SUID/不明原因猝死（SUDP）相关。43个基因可被归类为心脏基因，与心肌病、心律失常和其他病症有关。22个基因中的变异与神经功能相关。在13个据报道对各种全身性疾病具有致病性的基因中也发现了变异。8个基因中的变异与缺氧反应以及活性氧（ROS）的调节有关，此前在SIDS/SUID/SUDP中尚未有过描述。72名婴儿符合三重风险假说标准（图1）。
我们的研究证实并进一步扩展了与SUID相关的遗传变异列表。与心脏病相关的基因丰富以及与氧化还原代谢相关的变异的发现，对SUID的病理生理学具有重要的机制意义。
