Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy
Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy
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DOI：
10.1038/ejhg.2008.208
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发表时间：
2009-04-01
影响因子：
5.2
通讯作者：
de Brouwer, Arjan P. M.
中科院分区：
文献类型：
--
作者：
Lugtenberg, Dorien;Kleefstra, Tjitske;de Brouwer, Arjan P. M.
在严重精神发育迟滞、婴儿肌张力减退、进行性痉挛和复发性感染的患者中描述了涉及MECP 2的Xq28重复。然而，目前尚不清楚这些症状和伴随症状可能会在多大程度上发生变化。此外，Xq28重复的频率，包括MECP2尚未确定在不明原因的X连锁精神发育迟滞患者和（铁）男性严重脑病。在这项研究中，我们使用多重连接依赖性探针扩增来筛选这些患者队列中Xq28（包括MECP2）的缺失和重复。在283例X连锁精神发育迟滞患者中，我们发现了3个Xq28重复，包括MECP2，这表明大约1%的原因不明的X连锁精神发育迟滞可能是由MECP2重复引起的。此外，我们在134名患有精神发育迟滞和严重（大多为进行性）神经系统症状的男性患者中发现了另外三个MECP 2重复，表明该组患者的突变频率可能高达2%。在329例女性患者中，未检测到Xq28重复。总之，我们评估了13名男性患者与MECP2重复6个无关的家庭。中度至重度精神发育迟滞和儿童肌张力减退在所有患者中注意到。大多数患者还表现为言语缺失、癫痫发作和进行性痉挛以及共济失调或共济失调步态和脑萎缩，这两种症状以前未报告。我们建议在所有伴有（进行性）神经系统症状的中度至重度精神发育迟滞男性的当前诊断检测中实施MECP2的DNA拷贝数检测。
Duplications in Xq28 involving MECP2 have been described in patients with severe mental retardation, infantile hypotonia, progressive spasticity, and recurrent infections. However, it is not yet clear to what extent these and accompanying symptoms may vary. In addition, the frequency of Xq28 duplications including MECP2 has yet to be determined in patients with unexplained X-linked mental retardation and (fe) males with severe encephalopathy. In this study, we used multiplex ligation-dependent probe amplification to screen Xq28 including MECP2 for deletions and duplications in these patient cohorts. In the group of 283 patients with X-linked mental retardation, we identified three Xq28 duplications including MECP2, which suggests that approximately 1% of unexplained X-linked mental retardation may be caused by MECP2 duplications. In addition, we found three additional MECP2 duplications in 134 male patients with mental retardation and severe, mostly progressive, neurological symptoms, indicating that the mutation frequency could be as high as 2% in this group of patients. In 329 female patients, no Xq28 duplications were detected. In total, we assessed 13 male patients with a MECP2 duplication from six unrelated families. Moderate to severe mental retardation and childhood hypotonia was noted in all patients. The majority of the patients also presented with absent speech, seizures, and progressive spasticity as well as ataxia or an ataxic gait and cerebral atrophy, two previously unreported symptoms. We propose to implement DNA copy number testing for MECP2 in the current diagnostic testing in all males with moderate to severe mental retardation accompanied by (progressive) neurological symptoms.