Diagnosis and Development, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Parkville, 3052, Australia; Faculty of Medicine, Dentistry and Health Sciences, Department of Paediatrics, University of Melbourne, Parkville, 3052, Australia; School of Psychology and Public Health, La Trobe University, Melbourne, 3083, Australia.
Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
Eur J Med Genet. 2022 Apr;65(4):104456. doi: 10.1016/j.ejmg.2022.104456. Epub 2022 Feb 23.
Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by loss of expression of the maternally-inherited UBE3A on chromosome 15q11.2. In AS due to a chromosomal deletion that encompasses UBE3A, paternal uniparental disomy of chromosome 15, or imprinting defects (ImpD), the SNRPN locus is unmethylated, while in neurotypical individuals, it is ∼50% methylated. We present the developmental profile of two adults with mild AS assessed using standardized behavioral and neurodevelopmental measures. Both had intellectual disability with unusually advanced verbal communication skills compared to other individuals with AS. Methylation of the SNRPN locus was examined using Methylation Specific Quantitative Melt Analysis (MS-QMA) in different tissues at one time point for participant A (22 years) and two time points for participant B (T1: 22 years, T2: 25 years), and these levels were compared to a typical AS cohort. While participant A showed methylation levels comparable to the typical AS cohort, participant B showed methylation mosaicism in all tissues at both time points and changes in methylation levels from T1 to T2. AS should be considered in individuals with intellectual disability and verbal speech who may not have the typical symptoms of AS.
天使综合征（AS）是一种严重的神经发育障碍，由 15 号染色体上母系来源的 UBE3A 表达缺失引起。在由于染色体缺失、包含 UBE3A 的父源单亲二体性或印迹缺陷（ImpD）导致的 AS 中，SNRPN 基因座未甲基化，而在神经典型个体中，其约 50%被甲基化。我们介绍了使用标准化行为和神经发育测量评估的两名轻度 AS 成年患者的发育情况。这两名患者均存在智力障碍，但与其他 AS 患者相比，他们的言语交流能力异常先进。使用甲基化特异性定量熔解分析（MS-QMA）在参与者 A（22 岁）的一个时间点和参与者 B（T1：22 岁，T2：25 岁）的两个时间点检查了 SNRPN 基因座的甲基化情况，并将这些水平与典型 AS 队列进行了比较。虽然参与者 A 的甲基化水平与典型 AS 队列相当，但参与者 B 在两个时间点的所有组织中均表现出甲基化镶嵌现象，并且 T1 到 T2 的甲基化水平发生了变化。对于存在智力障碍和言语的个体，如果没有典型的 AS 症状，应考虑 AS 的可能性。
