Angelman syndrome (AS) is a genetic neurodevelopmental disorder caused by loss or deficient expression of UBE3A on the maternally inherited allele. In 10–15% of individuals with a clinical diagnosis of AS, a molecular diagnosis cannot be established with conventional testing. We describe a 13‐year‐old male with an atypical presentation of AS, who was found to have a novel, maternally inherited, intronic variant in UBE3A (c.3‐12T>A) using genome sequencing (GS). Targeted sequencing of RNA isolated from blood confirmed the creation of a new acceptor splice site. These GS results ended a six‐year diagnostic odyssey and revealed a 50% recurrence risk for the unaffected parents. This case illustrates a previously unreported splicing variant causing AS. Intronic variants identifiable by GS may account for a proportion of individuals who are suspected of having well‐known genetic disorders despite negative prior genetic testing.

中文翻译：

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UBE3A的一个新的内含子变体，通过非典型表现的安格曼综合征患者进行基因组测序鉴定。

Angelman综合征（AS）是遗传性神经发育障碍，由母本遗传的等位基因上UBE3A的表达缺失或不足引起。在有10-15％的临床诊断为AS的个体中，常规检测无法确定分子诊断。我们描述了一位13岁的男性，具有非典型的AS表现，该男性在UBE3A中发现了一种新的，母系遗传的内含子变体（c.3-12T> A）使用基因组测序（GS）。从血液中分离的RNA的靶向测序证实了新的受体剪接位点的创建。这些GS结果结束了为期六年的诊断旅程，并发现未患病父母的复发风险为50％。这种情况说明了以前未报告的导致AS的剪接变体。GS可鉴定的内含子变体可能占尽管事先基因测试阴性但仍被怀疑患有众所周知的遗传疾病的个体比例。