Data from: A quantitative electrophysiological biomarker of duplication 15q11.2-q13.1 syndrome

Background: Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism spectrum disorder (ASD). A distinct electrophysiological (EEG) pattern characterized by excessive activity in the beta band has been noted in clinical reports. We asked whether EEG power in the beta band, as well as in other frequency bands, distinguished children with Dup15q syndrome from those with non-syndromic ASD and then examined the clinical correlates of this electrophysiological biomarker in Dup15q syndrome.
Methods: In the first study, we recorded spontaneous EEG from children with Dup15q syndrome (n = 11), age-and-IQ-matched children with ASD (n = 10) and age-matched typically developing (TD) children (n = 9) and computed relative power in 6 frequency bands for 9 regions of interest (ROIs). Group comparisons were made using a repeated measures analysis of variance. In the second study, we recorded spontaneous EEG from a larger cohort of individuals with Dup15q syndrome (n = 27) across two sites and examined age, epilepsy, and duplication type as predictors of beta power using simple linear regressions.
Results: Spontaneous beta1 (12 – 20 Hz) and beta2 (20 – 30 Hz) power were significantly higher in Dup15q syndrome compared with both comparison groups, while delta (1 – 4 Hz) was significantly lower than both comparison groups. Effect sizes in all three frequency bands were large (|d| > 1). In the second study, we found that beta2 power was significantly related to epilepsy diagnosis in Dup15q syndrome.
Conclusions: Here, we have identified an electrophysiological biomarker of Dup15q syndrome that may facilitate clinical stratification, treatment monitoring, and measurement of target engagement for future clinical trials. Future work will investigate the genetic and neural underpinnings of this electrophysiological signature as well as the functional consequences of excessive beta oscillations in Dup15q syndrome.

背景：15q11.2-q13.1片段重复综合征（Dup15q syndrome）与自闭症谱系障碍（Autism Spectrum Disorder, ASD）的发病具有极高的外显率。临床研究中已观察到一种以β频段活动过度为特征的特异性脑电图（Electroencephalogram, EEG）表型。本研究旨在探究β频段及其他频段的脑电功率能否区分Dup15q综合征患儿与非综合征性自闭症谱系障碍患儿，并分析该电生理生物标志物在Dup15q综合征中的临床相关性。
方法：第一项研究中，我们采集了11例Dup15q综合征患儿、10例年龄与智商匹配的非综合征性自闭症谱系障碍患儿以及9例年龄匹配的典型发育（Typically Developing, TD）儿童的自发脑电信号，并针对9个感兴趣区（Regions of Interest, ROIs）计算6个频段的相对功率。组间比较采用重复测量方差分析。第二项研究中，我们在两个研究中心采集了27例更大队列的Dup15q综合征患者的自发脑电信号，并通过简单线性回归分析，以年龄、癫痫病史及重复片段类型作为β功率的预测因子。
结果：与两个对照组相比，Dup15q综合征患儿的β1（12–20 Hz）及β2（20–30 Hz）功率显著升高，而δ（1–4 Hz）功率则显著低于两个对照组。三个频段的效应量均较大（|d| > 1）。第二项研究发现，β2功率与Dup15q综合征患者的癫痫诊断显著相关。
结论：本研究鉴定出一种可用于Dup15q综合征的电生理生物标志物，其或可助力未来临床试验中的临床分层、治疗监测以及靶点参与度评估。后续研究将进一步探究该电生理特征的遗传与神经机制，以及Dup15q综合征中β振荡过度的功能后果。