Le Fevre Anna, Beygo Jasmin, Silveira Cheryl, Kamien Benjamin, Clayton-Smith Jill, Colley Alison, Buiting Karin, Dudding-Byth Tracy
Hunter Genetics, Newcastle, Australia.
Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Germany.
Am J Med Genet A. 2017 Mar;173(3):753-757. doi: 10.1002/ajmg.a.38072.
Angelman syndrome (AS) is characterized by severe intellectual disability, limited, or absent speech and a generally happy demeanor. The four known etiological mechanisms; deletions, uniparental disomy, imprinting defects, and UBE3A mutation all affect expression of the UBE3A gene at 15q11-q13. An atypical phenotype is seen in individuals who are mosaic for a chromosome 15q11-q13 imprinting defect on the maternal allele. These patients present with a milder phenotype, often with hyperphagia and obesity or non-specific intellectual disability. Unlike typical AS syndrome, they can have a vocabulary up to 100 words and speak in sentences. Ataxia and seizures may not be present, and the majority of individuals do not have microcephaly. Here we review the current literature and present three individuals with atypical AS caused by a mosaic imprinting defect to demonstrate why DNA methylation analysis at the SNRPN locus needs to be considered in a broader clinical context. © 2017 Wiley Periodicals, Inc.
安吉尔曼综合征（AS）的特征是严重智力残疾、言语有限或缺失，以及总体上愉快的举止。四种已知的病因机制，即缺失、单亲二体、印记缺陷和UBE3A突变，均会影响位于15q11 - q13的UBE3A基因的表达。在母本等位基因上存在15号染色体q11 - q13印记缺陷的嵌合体个体中可观察到非典型表型。这些患者表现出较轻微的表型，常伴有贪食和肥胖或非特异性智力残疾。与典型的AS综合征不同，他们的词汇量可达100个单词并能说出句子。可能不存在共济失调和癫痫发作，且大多数个体没有小头畸形。在此，我们回顾当前文献，并展示三名由嵌合印记缺陷导致非典型AS的个体，以说明为何需要在更广泛的临床背景下考虑对SNRPN基因座进行DNA甲基化分析。© 2017威利期刊公司
