Diurnal variation in autonomic regulation among patients with genotyped Rett syndrome.
Diurnal variation in autonomic regulation among patients with genotyped Rett syndrome.
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DOI：
10.1136/jmedgenet-2019-106601
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发表时间：
2020-11
影响因子：
4
通讯作者：
Weese-Mayer DE
中科院分区：
文献类型：
--
作者：
Carroll MS;Ramirez JM;Weese-Mayer DE
Rett 综合征是一种严重的神经系统疾病，具有一系列致残性自主神经和呼吸系统症状，主要由 X 染色体长臂上的甲基 CpG 结合蛋白 2 基因变异引起。随着基础研究开始提出潜在的治疗方法，需要对动态表型进行灵敏的测量来评估这些研究工作的结果。在这里，我们检验了这样的假设：自然环境中雷特综合征的生理指纹与对照组不同，并且雷特综合征内的基因型之间也存在差异。根据 47 个病例和匹配对照的夜间和白天家庭动态记录的现有数据库，对一系列全面的心率变异性、心肺耦合和心脏复极测量进行了评估。患有雷特综合征的女孩和匹配的对照组之间的差异在一系列自主神经测量中很明显，并表明交感神经激活和/或副交感神经失活的转变。在昼夜节律背景下分析的每日时间趋势揭示了自主平衡昼夜模式的幅度和相位的变化。按基因型类别进行的进一步分析证实了 Rett 综合征表型的分级表现，其中早期截短突变的患者与对照组的差异最大，而晚期截短突变和错义突变的患者与对照组的差异最小。通过广泛的家庭生理测量进行综合自主神经测量可以检测患有雷特综合征的女孩表型的细微变化，这表明这些技术适合指导新疗法。
Rett syndrome is a severe neurological disorder with a range of disabling autonomic and respiratory symptoms and resulting predominantly from variants in the methyl-CpG binding protein 2 gene on the long arm of the X-chromosome. As basic research begins to suggest potential treatments, sensitive measures of the dynamic phenotype are needed to evaluate the results of these research efforts. Here we test the hypothesis that the physiological fingerprint of Rett syndrome in a naturalistic environment differs from that of controls, and differs among genotypes within Rett syndrome. A comprehensive array of heart rate variability, cardiorespiratory coupling and cardiac repolarisation measures were evaluated from an existing database of overnight and daytime inhome ambulatory recordings in 47 cases and matched controls. Differences between girls with Rett syndrome and matched controls were apparent in a range of autonomic measures, and suggest a shift towards sympathetic activation and/or parasympathetic inactivation. Daily temporal trends analysed in the context of circadian rhythms reveal alterations in amplitude and phase of diurnal patterns of autonomic balance. Further analysis by genotype class confirms a graded presentation of the Rett syndrome phenotype such that patients with early truncating mutations were most different from controls, while late truncating and missense mutations were least different from controls. Comprehensive autonomic measures from extensive inhome physiological measurements can detect subtle variations in the phenotype of girls with Rett syndrome, suggesting these techniques are suitable for guiding novel therapies.
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