Relationships between UBE3A and SNORD116 expression and features of autism in chromosome 15 imprinting disorders.
Relationships between UBE3A and SNORD116 expression and features of autism in chromosome 15 imprinting disorders.
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DOI：
10.1038/s41398-020-01034-7
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发表时间：
2020-10-29
影响因子：
6.8
通讯作者：
Godler DE
中科院分区：
文献类型：
--
作者：
Baker EK;Butler MG;Hartin SN;Ling L;Bui M;Francis D;Rogers C;Field MJ;Slee J;Gamage D;Amor DJ;Godler DE
15 号染色体 (C15) 印记疾病，包括 Prader–Willi (PWS)、Angelman (AS) 和 15 号染色体重复 (Dup15q) 综合征，是由 15q11–q13 区域基因表达异常引起的严重神经发育障碍，与异常 DNA 甲基化和/或拷贝数变化相关。本研究比较了这些疾病及其亚型之间位于 15q11-q13 区域内的 UBE3A 和 SNORD116 mRNA 水平的变化，并将这些变化与临床表型相关联。研究队列包括 58 名患有 C15 印记障碍的参与者（PWS = 27、AS = 21、Dup15q = 10）和 20 名典型发育对照。使用逆转录液滴数字聚合酶链反应 (PCR) 对外周血单核细胞 (PBMC) 的 mRNA 进行半定量分析，对 UBE3A 和 SNORD116 进行标准化，并根据使用 geNorm 方法确定的一组内部对照基因进行归一化。参与者完成了智力/发育功能评估和自闭症诊断观察表第二版。与对照组相比，Dup15q 组是唯一 UBE3A mRNA 水平显着升高的组 (p<0.001)。与对照组相比，AS 组和 Dup15q 组的 SNORD116 mRNA 水平也显着升高（AS：p < 0.0001；Dup15q：p = 0.002）。 UBE3A 和 SNORD116 mRNA 水平与缺失 AS 组的所有发育功能评分 (p<0.001) 以及非缺失 PWS 组的自闭症特征 (p<0.001) 呈正相关。研究结果表明，PBMC 中 UBE3A 和 SNORD116 的表达与这些疾病中运动和语言障碍以及自闭症特征背后的大脑特定过程之间存在新的相互作用。
Chromosome 15 (C15) imprinting disorders including Prader–Willi (PWS), Angelman (AS) and chromosome 15 duplication (Dup15q) syndromes are severe neurodevelopmental disorders caused by abnormal expression of genes from the 15q11–q13 region, associated with abnormal DNA methylation and/or copy number changes. This study compared changes in mRNA levels of UBE3A and SNORD116 located within the 15q11–q13 region between these disorders and their subtypes and related these to the clinical phenotypes. The study cohort included 58 participants affected with a C15 imprinting disorder (PWS = 27, AS = 21, Dup15q = 10) and 20 typically developing controls. Semi-quantitative analysis of mRNA from peripheral blood mononuclear cells (PBMCs) was performed using reverse transcription droplet digital polymerase chain reaction (PCR) for UBE3A and SNORD116 normalised to a panel of internal control genes determined using the geNorm approach. Participants completed an intellectual/developmental functioning assessment and the Autism Diagnostic Observation Schedule-2nd Edition. The Dup15q group was the only condition with significantly increased UBE3A mRNA levels when compared to the control group (p < 0.001). Both the AS and Dup15q groups also had significantly elevated SNORD116 mRNA levels compared to controls (AS: p < 0.0001; Dup15q: p = 0.002). Both UBE3A and SNORD116 mRNA levels were positively correlated with all developmental functioning scores in the deletion AS group (p < 0.001), and autism features (p < 0.001) in the non-deletion PWS group. The findings suggest presence of novel interactions between expression of UBE3A and SNORD116 in PBMCs and brain specific processes underlying motor and language impairments and autism features in these disorders.
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影响因子：
4.9
作者：
Baker, Emma K.;Godler, David E.;Bretherton, Lesley
通讯作者：
Bretherton, Lesley
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作者：
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