Duplication of the 15q11-q13 region: Clinical and genetic study of 30 new cases
Duplication of the 15q11-q13 region: Clinical and genetic study of 30 new cases
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DOI：
10.1016/j.ejmg.2013.10.008
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发表时间：
2014-01-01
影响因子：
1.9
通讯作者：
Verloes, Alain
中科院分区：
文献类型：
--
作者：
Al Ageeli, Essam;Drunat, Severine;Verloes, Alain
背景资料：15 q11-q13区域是已知的基因组重排易感区域，其中已经鉴定出几个断裂点（BP 1-BP 5）。在两种情况下观察到该区域的重复：存在源自15号染色体的额外标记染色体（SMC）或间质串联重复。重复的临床特点是一个可变的表型，包括中枢性肌张力减退，发育迟缓，言语迟缓，癫痫发作，轻微畸形的特点和autosit.Methods：回顾性临床和分子研究的30名无关的患者中发现的患者在遗传诊所的罗伯特DEBRE医院与微重复的15 q11-q13区域。15例患者出现了来自15号染色体的额外标记。在14例病例中，SMC尺寸较大，包括Prader-Willi/Angelman临界区域。除一个外，其他都是母亲的血统。1例患者在没有母体UPD的情况下具有PWS样表型。在一种情况下，标记物具有较小的尺寸并且仅包含BP 1-BP 2区域。15例患者出现间质性重复畸形。4例遗传自表型正常的父母（3例母亲和1例父亲）。表型特征有些变化，57%的人患有自闭症。12例患者显示大脑异常，18例患者脑电图异常，清醒记录中出现典型的可识别模式，即过度弥散性快速尖峰，与苯二氮卓类药物暴露后观察到的模式相似。两名自闭症患者中父本表达的基因MKRN 3、MAGEL 2和NDN的复制，没有邻近区域的额外材料，增加了它们是与自闭症相关基因的可能性。(C)2013年Elsevier Masson SAS。All rights reserved.
Background: 15q11-q13 region is an area of well-known susceptibility to genomic rearrangements, in which several breakpoints have been identified (BP1-BP5). Duplication of this region is observed in two instances: presence of a supernumerary marker chromosome (SMC) derived of chromosome 15, or interstitial tandem duplication. Duplications are clinically characterized by a variable phenotype that includes central hypotonia, developmental delay, speech delay, seizure, minor dysmorphic features and autism.Methods: Retrospective clinical and molecular study of 30 unrelated patients who were identified among the patients seen at the genetic clinics of Robert DEBRE hospital with microduplication of the 15q11-q13 region.Results: Fifteen patients presented with a supernumerary marker derived from chromosome 15. In fourteen cases the SMC was of large size, encompassing the Prader-Willi/Angelman critical region. All but one was maternal in origin. One patient had a PWS-like phenotype in absence of maternal UPD. In one case, the marker had a smaller size and contained only the BP1-BP2 region. Fifteen patients presented with interstitial duplication. Four cases were inherited from phenotypically normal parents (3 maternal and 1 paternal). Phenotypic features were somewhat variable and 57% presented with autism. Twelve patients showed cerebral anomalies and 18 patients had an abnormal EEG with a typical, recognizable pattern of excessive diffuse rapid spikes in the waking record, similar to the pattern observed after benzodiazepine exposure. Duplication of paternally expressed genes MKRN3, MAGEL2 and NDN in two autistic patients without extra material of a neighboring region enhances their likelihood to be genes related to autism. (C) 2013 Elsevier Masson SAS. All rights reserved.