一例典型的Rett综合征患儿MECP2基因分子遗传学研究  

Molecular genetic study of MECP2 gene for a patient with typical Rett syndrome

作　　者：朱海燕[1] 胡娅莉[1] 朱瑞芳[1] 杨滢[1] 朱湘玉[1] 王皖骏[1] 段红蕾[1] 

机构地区：[1]南京大学医学院附属鼓楼医院妇产科产前诊断中心遗传室,210008

出　　处：《中华医学遗传学杂志》2011年第6期625-629,共5页Chinese Journal of Medical Genetics

基　　金：基金项目：江苏省“六大人才高峰”资助项目（2008-D30）;南京市医学科技发展重大项目（基因病产前诊断技术平台的建立）

摘　　要：目的通过对甲基化CpG结合蛋白2（methyl—CpGbindingprotein2，MECP2）基因的分子遗传学分析，对l例典型的Rett综合征患儿进行基因诊断，为罹患家庭提供遗传咨询。方法综合应用序列分析及多重连接依赖性探针扩增（multiplexligation-dependentprobeamplification，MLPA）对MECP2基因进行突变分析，同时对患儿进行核型分析以排除染色体异常。结果患儿核型正常。针对MECP2基因各外显子的序列分析未发现MECP2基因序列的变异，但在1名正常女性对照中检测到该基因第4外显子序列的杂合改变（C．1072G〉A），随后对其子女进行了相应序列分析，其儿子检测到纯合变异，其女儿检测到相同的杂合变异，其他对照未检测到该变异。经MLPA检测发现，患儿MECP2基因的第3、4外显子部分区域缺失，应用cDNA的扩增和序列分析，发现患儿MECP2基因存在1176个碱基的缺失（e．27—1202delll76），其父母未检测到该突变。结论对于经过常规序列分析未发现MECP2突变的典型Rett综合征患儿，用MLPA检测将有助于发现大片段的缺失突变，结合cDNA的序列分析，将有望明确其断裂点。Objective To provide genetic diagnosis and counseling for a 2-year-old girl with typical Rett syndrome through analyzing the methyl-CpG binding protein 2 （MECP2） gene. Methods Potential mutation of the MECP2 gene was screened by DNA sequencing and multiplex ligation-dependent probe amplification （MLPA） analysis of members of the family as well as normal controls. Lymphocyte culture for karyotype analysis was carried out for the patient to exclude chromosomal abnormalities. Results The karyotype of the girl was normal. No variation of the MECP2 gene was detected in the patient by direct sequencing. A heterozygosis variation, c. 1072G^A in exon 4 of the MECP2 gene was detected in a normal female control, which was not found in other controls. The son and daughter of the female control were respectively heterozygous and homozygous carriers of the same mutation. By MLPA analysis, a heterozygosis deletion of exon 3 and part of exon 4 was detected in the patient, cDNA amplification and sequencing confirmed the presence of a 1176 bp deletion （c. 27-1202de11176）. The same deletion was not detected in the parents. Conclusion A large deletion in MECP2 gene was detected with MLPA in a patient featuring typical Rett syndrome. The same deletion was missed by sequencing analysis. With cDNA sequencing, the breakage point of the mutation can be mapped precisely mapped.

关 键 词：RETT综合征 MECP2基因 缺失 突变 基因诊断 

分 类 号：R725.9[医药卫生—儿科]