15q11.2 Duplication Encompassing Only the UBE3A Gene Is Associated with Developmental Delay and Neuropsychiatric Phenotypes
15q11.2 Duplication Encompassing Only the UBE3A Gene Is Associated with Developmental Delay and Neuropsychiatric Phenotypes
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DOI：
10.1002/humu.22800
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发表时间：
2015-07-01
期刊：
影响因子：
3.9
通讯作者：
Stavropoulos, Dimitri J.
中科院分区：
文献类型：
--
作者：
Noor, Abdul;Dupuis, Lucie;Stavropoulos, Dimitri J.
带有母体印记的染色体区域 15q11-q13 的重复与多种神经精神疾病有关，包括自闭症谱系障碍、发育迟缓、学习困难、精神分裂症和癫痫发作。这些观察结果表明，该区域内存在一个或多个剂量敏感的印记基因，这解释了神经精神表型风险增加的原因。我们介绍了一名发育迟缓的女性患者，我们在该患者的染色体区域 15q11.2 中发现了母系遗传的 129-Kb 重复，仅包含 UBE3A 基因。培养的成纤维细胞的表达分析证实，与年龄和性别匹配的对照相比，先证者中 UBE3A 过度表达。我们进一步测试了四代中这种重复的分离，发现它与神经精神表型分离。我们的研究首次显示了与人类 UBE3A 过度表达相关的临床特征，并强调了该基因在 15q11-q13 重复个体表型中的重要性。 (C) 2015 年 Wiley 期刊公司。
Duplications of chromosome region 15q11-q13 with the maternal imprint are associated with a wide spectrum of neuropsychiatric disorders, including autism spectrum disorders, developmental delay, learning difficulties, schizophrenia, and seizures. These observations suggest there is a dosage-sensitive imprinted gene or genes within this region that explains the increased risk for neuropsychiatric phenotypes. We present a female patient with developmental delay in whom we identified a maternally inherited 129-Kb duplication in chromosome region 15q11.2 encompassing only the UBE3A gene. Expression analysis in cultured fibroblasts confirmed overexpression of UBE3A in the proband, compared with age- and sex-matched controls. We further tested segregation of this duplication in four generations and found it segregated with neuropsychiatric phenotypes. Our study shows for the first time clinical features associated with overexpression of UBE3A in humans and underscores the significance of this gene in the phenotype of individuals with 15q11-q13 duplication. (C) 2015 Wiley Periodicals, Inc.