Wink Logan K, Fitzpatrick Sarah, Shaffer Rebecca, Melnyk Sophia, Begtrup Amber H, Fox Emma, Schaefer Tori L, Mathieu-Frasier Lauren, Ray Balmiki, Lahiri Debomoy, Horn Paul A, Erickson Craig A
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Indiana University School of Medicine, Indianapolis, Indiana.
Am J Med Genet A. 2015 Nov;167A(11):2623-8. doi: 10.1002/ajmg.a.37254. Epub 2015 Jul 29.
Angelman Syndrome (AS) is a rare neurodevelopmental disorder associated with developmental delay, speech impairment, gait ataxia, and a unique behavioral profile. AS is caused by loss of maternal expression of the paternally imprinted UBE3A gene. In this study we aim to contribute to understanding of the neurobehavioral phenotype of AS with particular focus on the neuropsychiatric presentation of the disorder. We also undertake initial exploration of brain-derived neurotrophic factor (BDNF) plasma levels in AS. Twelve individuals ages 3 years or older with a confirmed genetic diagnosis of AS underwent detailed medical history, phenotypic characterization, and BDNF plasma sampling. The results of this study demonstrate that individuals with AS suffer from significant developmental delay, impaired adaptive behavior, and sleep disruption. Additionally, hyperactivity/impulsivity appears to be the primary behavioral domain noted in these individuals. The majority of individuals in this project met criteria for autism spectrum disorder on the Autism Diagnostic Observation Schedule (ADOS); however, a negative correlation was noted between ADOS score and developmental age. BDNF plasma levels in AS individuals were significantly elevated compared to neurotypical controls. This is the first report of abnormal BDNF levels in AS, and one that necessitates larger future studies. The results provide a clue to understanding abnormal neuronal development in AS and may help guide future AS research.
天使综合征（AS）是一种罕见的神经发育障碍，与发育迟缓、言语障碍、步态共济失调以及独特的行为特征有关。AS是由父系印记的UBE3A基因的母源表达缺失引起的。在本研究中，我们旨在促进对AS神经行为表型的理解，特别关注该疾病的神经精神表现。我们还对AS患者血浆中脑源性神经营养因子（BDNF）水平进行了初步探索。12名年龄在3岁及以上且经基因确诊为AS的个体接受了详细的病史询问、表型特征分析以及BDNF血浆样本采集。本研究结果表明，AS患者存在显著的发育迟缓、适应性行为受损以及睡眠障碍。此外，多动/冲动似乎是这些个体中主要的行为表现领域。该项目中的大多数个体在自闭症诊断观察量表（ADOS）上符合自闭症谱系障碍的标准；然而，ADOS评分与发育年龄之间存在负相关。与神经典型对照组相比，AS个体的BDNF血浆水平显著升高。这是关于AS患者BDNF水平异常的首次报告，未来需要进行更大规模的研究。这些结果为理解AS中异常的神经元发育提供了线索，并可能有助于指导未来的AS研究。
