目的 分析典型的Rett综合征患者的临床特点，并对患儿甲基化CpG结合蛋白-2（MECP2）基因进行突变分析。方法 使用PCR扩增和测序的方法 对近期诊断的9例RETT综合征患儿及其父母MECP2基因的3个外显子进行检测。结果 在9例患儿中发现5例存在MECP2基因的杂合突变，突变率超过50%，其中1例为碱基插入导致的移码突变（c.913insT）；其余4例为点突变，分别为位于外显子3的c.316C>T（R106W），位于外显子4的c.502C>T（R168X）、c.808C>T（R270X）和c.1126C>T（P376S），其中c.913insT为首次发现的突变，这些患儿父母均未检测到突变。2例患儿MECP2基因突变位于转录抑制区域，与其他患儿相比，这2个患儿语言功能几乎丧失，且发育明显落后。结论 该研究确诊的5例Rett综合征的患儿存在MECP2基因突变，且多数位于外显子4上；MECP2蛋白转录抑制区域突变可能影响患儿语言功能及发育明显落后。
Abstract
Objective To study the clinical features and mutations in methyl-CpG-binding protein 2 (MECP2) gene among children with classical Rett syndrome in China. Methods PCR and direct sequencing were employed to analyze the three exons of MECP2 gene in 9 children recently diagnosed with Rett syndrome and their parents. Results Heterozygous mutations were identified in 5 out of 9 patients, with a mutation rate of over 50%; there was one case of insert mutation (c.913insT) and 4 cases of missense mutation (exon 3: c.316C>T (R106W); exon 4: c.502C>T (R168X), c.808C>T (R270X), and c.1126C>T (P376S)). A new mutation (c.913insT) was found. No mutations were detected in their parents. Two patients had MECP2 mutations in the transcriptional repression domain (TRD). They had almost lost language functions and were found to have significantly delayed development compared with other patients. Conclusions Mutations in MECP2 gene were detected in 5 confirmed cases of Rett syndrome, and most of them were on exon 4. Mutations in the TRD of MECP2 protein may affect the language ability and development in children with Rett syndrome.
关键词
Rett综合征 /
MECP2基因 /
突变 /
儿童
Key words
Rett syndrome /
MECP2 gene /
Mutation /
Child
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参考文献
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