中文摘要：

目的了解Rett综合征（RTT）患儿甲基化CpG结合蛋白2基因（MECP2）和细胞周期依赖性激酶样5蛋白基因（CDKL5）突变及热点突变，建立适合临床诊断的检测方法和策略。方法对1987至2007年北京大学第一医院儿科神经专业组诊断的177例散发RTT患儿抽取外周抗凝血提取DNA，用PCR—DNA测序方法对MECP2的全部外显子进行突变筛查，如未发现突变，用多重连接依赖的探针扩增（MLPA）法进行基因剂量分析。对MECP2未发现突变的患儿用变性高效液相色谱法（DHPLC）进行CDKL5突变筛查。结果在177例患儿中发现145例MECP2突变，1例CDKL5突变，总的突变率82％。MECP2突变中错义突变频率最高（39％）；其后依次为无义（28％）、移码（17％）和大片段缺失突变（14％）。所有突变中8种最常见突变依次为P．T158M（13％）、pR168X（12％）、c．806delG（7％）、p.R255X（6％）、p.R270X和p.R133C各（5％）、p.R306C（4％）、p.R106W（3％）。11％的患儿存在一个或多个外显子的缺失。结论中国R1T患儿MECP2突变谱和国外报道相似，有热点突变。c．806delG是中国人群特有的一个热点突变。

英文摘要：

Objective To study the spectrum of mutations in methyl-CpG-binding protein 2 gene （MECP2） and cyclin-dependent kinase-like 5 gene （CDKI3） in Chinese pediatric patients with Rett syndrome （RTT）, and establish a simple, quick, and efficient gene test method as well as screen a strategy of genetic diagnosis for RTT. Methods Genomic DNA was extracted using standard procedures from the peripheral blood leukocytes of 117 pediatric patients diagnosed from 1987 to 2007 . PCR was used to amplify the exons 1 - 4 of MECP2 using published primers. If no mutation was identified after screening exons 2 - 4, exon 1 was screened. If no mutation was identified in MECP2 by sequencing, multiplex ligation dependent probe amplification （MLPA） was employed to screen for large deletions by using P015C kit. If no mutation was identified in the MECP2 by sequencing and MLPA respectively, then the coding region of CDKL5 was screened by denaturing high performance liquid chromatography （DHPLC）. Results The total mutation frequency in MECP2 and CDKL5 genes among all RTT patients was 82%. MECP2 mutations were found in 86% （137/159） of the patients with classical RTT and in 44% （8/18） of those with atypical RTT. Most of the mutations were missense mutations, accounting for 39%, followed in order of frequency by nonsense mutations 28%, frame shift mutations 17% and large deletions 14. 5%. The eight most frequent MECP2 mutations were p. T158M （ 13% ）, p. R168X （ 12% ）, c. 806delG （7%）, p. R255X （6%）, p. R270X （5%）, p. R133C （5%）, p. R306C （4%）, and p. R106W （3%）, with p. T158M as the most common of the MECP2 mutations and c. 806delG as a hotspot mutation in Chinese patients with RTY. Only one synonymous mutation was identified in CDKLS. Conclusion The spectrum of MECP2 mutations within the mainland Chinese RTI＂ patients is similar to that of those patients reported in the world, p. T158M, p. R168X, c. 806delG, p. R255X, p. R270X, p. R133C, p. R306C, and p. R106W are the hotspot mutati