Genetic burden and associations with adverse neurodevelopment in neonates with congenital heart disease
Genetic burden and associations with adverse neurodevelopment in neonates with congenital heart disease
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DOI：
10.1016/j.ahj.2018.03.021
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发表时间：
2018-07-01
影响因子：
4.8
通讯作者：
Winlaw, David S.
中科院分区：
文献类型：
--
作者：
Blue, Gillian M.;Ip, Eddie;Winlaw, David S.
背景资料：多达20%的先天性心脏病（CHD）患儿接受心脏手术后会出现神经发育障碍（NDD），一些研究报告称存在持续性损伤。最近的大规模研究表明，CHD和NDD有共同的遗传机制。在这项研究中，有针对性的方法被应用到评估直接的临床适用性，这information.Methods：一个基因面板，包括148个已知的CHD和/或NDD基因被用来测序15例CHD + NDD，15例CHD患者，和15名健康对照。结果：CHD+ NDD组与对照组相比，罕见（次要等位基因频率< 0.01）和新变异显著增加，P
Background: Up to 20% of children with congenital heart disease (CHD) undergoing cardiac surgery develop neurodevelopmental disabilities (NDD), with some studies reporting persistent impairment. Recent large-scale studies have demonstrated shared genetic mechanisms contributing to CHD and NDD. In this study, a targeted approach was applied to assess direct clinical applicability of this information.Methods: A gene panel comprising 148 known CHD and/or NDD genes was used to sequence 15 patients with CHD + NDD, 15 patients with CHD, and 15 healthy controls. The number and types of variants between the 3 groups were compared using Poisson log-linear regression, and the SNP-set (Sequence) Kernel Association Test-Optimized was used to conduct single-gene and gene-pathway burden analyses.Results: A significant increase in rare (minor allele frequency < 0.01) and novel variants was identified between the CHD+ NDD cohort and controls, P