MECP2mutation spectrum and its clinical characteristics in a Chinese cohort
MECP2mutation spectrum and its clinical characteristics in a Chinese cohort
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中国队列MECP2突变谱及其临床特征
DOI：
10.1111/cge.13790
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发表时间：
2020-06-21
影响因子：
3.5
通讯作者：
Bao, Xinhua
中科院分区：
文献类型：
--
作者：
Wen, Yongxin;Wang, Jiaping;Bao, Xinhua
甲基cpg结合蛋白2 （MeCP2）功能障碍与多种神经系统疾病有关，其中以Rett综合征（RTT）最为突出。本研究以中国一例mecp2突变患者为研究对象，分析mecp2突变的特点及其临床表现。总共有666名患者被鉴定出126种不同的mecp2突变，其中包括22种新突变。超过80%的患者在第4外显子上携带mecp2突变。无义和错义突变是最常见的类型。错义突变主要发生在甲基- cpg结合域（MBD），无义突变主要发生在转录抑制域（TRD）和域间。大缺失的偏好位点是外显子3和/或外显子4。p.R133C、p.R294*、p.R306C和c -末端结构域（CTD）缺失的患者受影响较轻。不同突变组在行走能力、手功能和语言方面存在显著差异。3例mecp2突变女性患者（1例p.R306P， 2例p.R309W）仅表现为智力残疾/发育迟缓（ID/DD），未见明显RTT症状。本研究还发现了8例mecp2突变的男性个体，其中2例诊断为典型RTT， 3例诊断为非典型RTT， 3例诊断为ID/DD。
The dysfunction of methyl-CpG-binding protein 2 (MeCP2) is associated with several neurological disorders, of which Rett syndrome (RTT) is the most prominent. This study focused on a Chinese patient cohort withMECP2mutations, and analyzed the characteristics of these mutations and their clinical manifestations. In total, 666 patients were identified with 126 differentMECP2mutations, including 22 novel mutations. Over 80% of patients carried anMECP2mutation on exon 4. Nonsense and missense mutations were the most commonly reported types. Missense mutations were mainly located on methyl-CpG-binding domain (MBD), and nonsense mutations predominantly occurred on transcription repression domain (TRD) and inter domain. The predilection site of large deletion was exon 3 and/or exon 4. Patients with p.R133C, p.R294*, p.R306C, and C-terminal domain (CTD) deletions were less severely affected. Significant differences were found in ambulation ability, hand function, and language among different mutation groups. Three female patients withMECP2mutations (1 with p.R306P and 2 with p.R309W) only presented with intellectual disability/developmental delay (ID/DD), and no obvious RTT symptoms were reported. Eight male individuals withMECP2mutations were also identified in this study, including 2 diagnosed with typical RTT, 3 with atypical RTT and 3 with ID/DD.