Rett综合征患儿1例MECP2基因的突变鉴定及亲源性分析

Identification of MECP2 gene mutation in a child with Rett syndrome and its parental origin analysis

目的 鉴定1例Rett综合征(RTT)女孩的致病性突变及进行突变的亲源性分析.方法 收集中山大学中山医学院医学遗传学教研室1例典型RTT女孩的临床资料并进行综合分析.提取患儿及其父母的外周血DNA;PCR扩增MECP2基因的全部4个外显子及剪接位点序列,对PCR产物进行直接测序;利用患儿MECP2基因突变位点附近的SNP位点进行等位基因特异性PCR扩增并测序,进行突变的亲源性分析.结果 患儿携带了MECP2 c.502C>T(p.R168X)杂合性突变;患者的双亲该位点均为正常的C碱基.患儿MECP2基因第3内含子存在1个SNP c.378-74C>T(即rs2071569),患儿的c.502C>T突变来自父源X染色体.结论 MECP2 c.502C>T(p.R168X)杂合性突变为该患儿的致病性突变,突变来自父源,该研究为基因型-表型的研究及遗传咨询提供了重要的依据.

Objective To identify the pathogenic mutation in a girl with Rett syndrome(RTT), and to perform a parental origin analysis of the mutation. Methods The clinical data of a Chinese girl with typical RTT from the Department of Medical Genetics,School of Medicine,Sun Yat-sen University were collected and analyzed comprehensively. The DNA was extracted from peripheral blood of the child and her parents. All 4 exons and the intron-exon splice sites of MECP2 gene were amplified by polymerase chain reaction(PCR),and the PCR products were directly sequenced. Using the SNP loci near MECP2 gene mutation,allele-specific PCR amplification and sequencing was completed and thereby the parental origin analysis was performed. Results The child carried a heterozygous mutation c. 502C>T (p. R168X) in MECP2 gene. Both her parents showed normal C nucleotide at the same site. There was one SNP c.378-74C>T (ie rs2071569)in the third intron of the MECP2 gene in the child,and the c.502C>T mutation in the child was passed on from her father's X chromosome. Conclusion The heterozygous mutation of c. 502C>T(p. R168X)in MECP2 gene is a pathogenic mutation in this child,which was passed on from her father. This study provides an important evidence for genotype-phenotype research and genetic counseling.