Complex Segmental Duplications Mediate a Recurrent dup(X)(p11.22-p11.23) Associated with Mental Retardation, Speech Delay, and EEG Anomalies in Males and Females
Complex Segmental Duplications Mediate a Recurrent dup(X)(p11.22-p11.23) Associated with Mental Retardation, Speech Delay, and EEG Anomalies in Males and Females
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DOI：
10.1016/j.ajhg.2009.08.001
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发表时间：
2009-09-11
影响因子：
9.8
通讯作者：
Zuffardi, Orsetta
中科院分区：
文献类型：
--
作者：
Giorda, Roberto;Bonaglia, M. Clara;Zuffardi, Orsetta
亚显微拷贝数变异对人类疾病的遗传病因学做出了相当大的贡献。我们通过使用基于全基因组寡核苷酸的阵列比较基因组杂交 (aCGH) 分析了特发性精神发育迟滞 (MR) 受试者，并鉴定了患有 MR、言语延迟和儿童期特殊脑电图 (EEG) 模式的男性和女性中的家族性和从头复发性 Xp11.22-p11.23 重复。重复的大小范围为 0.8-9.2 Mb。大多数受影响的女性表现出复制 X 染色体的优先激活。最小重复的携带者表现出X连锁隐性遗传。所有其他受影响的个体均呈现显性表达和可比较的临床表型，无论性别、重复大小和 X 失活模式如何。大多数重排是由侧翼复杂片段重复之间的重组介导的。常见临床特征的识别，包括典型的脑电图模式、易感基因组结构和特殊的 X 失活模式，表明 Xp11.22-p11.23 的重复构成了一种先前未描述的综合征。
Submicroscopic copy-number variations make a considerable contribution to the genetic etiology of human disease. We have analyzed subjects with idiopathic mental retardation (MR) by using whole-genome oligonucleotide-based array comparative genomic hybridization (aCGH) and identified familial and de novo recurrent Xp11.22-p11.23 duplications in males and females with MR, speech delay, and a peculiar electroencephalographic (EEG) pattern in childhood. The size of the duplications ranges from 0.8-9.2 Mb. Most affected females show preferential activation of the duplicated X chromosome. Carriers of the smallest duplication show X-linked recessive inheritance. All other affected individuals present dominant expression and comparable clinical phenotypes irrespective of sex, duplication size, and X-inactivation pattern. The majority of the rearrangements are mediated by recombination between flanking complex segmental duplications. The identification of common clinical features, including the typical EEG pattern, predisposing genomic structure, and peculiar X-inactivation pattern, suggests that duplication of Xp11.22-p11.23 constitutes a previously undescribed syndrome.