Preserved expressive language as a phenotypic determinant of Mosaic Angelman Syndrome
Preserved expressive language as a phenotypic determinant of Mosaic Angelman Syndrome
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DOI：
10.1002/mgg3.837
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发表时间：
2019-08-10
影响因子：
2
通讯作者：
Duis, Jessica
中科院分区：
文献类型：
--
作者：
Carson, Robert P.;Bird, Lynne;Duis, Jessica
背景Angelman综合征（AS）是一种以智力障碍、言语障碍、运动障碍和独特的行为特征为核心特征的神经发育障碍。通常情况下，AS是由于UBE 3A的母体表达缺失而导致的，但有些个体的部分细胞存在印迹缺陷。这些个体对于正常和有缺陷的UBE 3A表达是嵌合的，导致嵌合AS（mAS），具有部分基因表达的损失。方法比较mAS与AS的表型。mAS的临床特征是从22例mAS患者的父母调查和Angelman自然史研究中获得的。这些与AS使用历史数据进行了对比。结果几乎所有的mAS患者都存在发育迟缓，而AS的核心特征报告率不到40%。虽然语言和管理日常生活活动的能力比AS患者的预期有明显改善，但mAS患者表现出较高的行为挑战发生率。结论：对发育迟缓、多动症、焦虑和异常快乐行为的个体进行临床检查，应促使甲基化研究排除mAS。我们扩大了AS的表型谱，包括与Prader-Willi重叠的功能，如摄食过多。
Background Angelman Syndrome (AS) is a neurodevelopmental disorder with core features of intellectual disability, speech impairment, movement disorders, and a unique behavioral profile. Typically, AS results from absent maternal expression of UBE3A, but some individuals have imprinting defects in a portion of their cells. These individuals are mosaic for normal and defective UBE3A expression, resulting in mosaic AS (mAS) with a partial loss of gene expression. Methods This study aims to contrast the mAS phenotype to that of AS. Clinical characteristics of mAS were obtained from a parental survey of 22 mAS patients and from the Angelman Natural History study. These were contrasted with those of AS using historical data. Results Developmental delay was present in nearly all mAS patients, whereas the core features of AS were reported in less than 40%. While language and ability to manage activities of daily living were markedly improved over that expected in AS, mAS patients demonstrated a high incidence of behavioral challenges. Conclusion Clinical work-up of an individual with developmental delay, hyperactivity, anxiety, and an uncharacteristically happy demeanor should prompt methylation studies to rule out mAS. We expand the phenotypic spectrum of AS to include features that overlap with Prader-Willi such as hyperphagia.