Rett综合征一个家系的胚胎植入前遗传学检测  

Preimplantation genetic testing for a Chinese pedigree affected with Rett syndrome

作　　者：段思琪 岳发贵[1] 杨潇[1] 刘睿智[1] 何晶[1] Duan Siqi;Yue Fagui;Yang Xiao;Liu Ruizhi;He Jing(Reproductive Medicine and Prenatal Diagnosis Center,the First Hospital of Jilin University,Changchun,Jilin 130021,China)

机构地区：[1]吉林大学第一医院生殖医学中心·产前诊断中心,长春130021

出　　处：《中华医学遗传学杂志》2024年第5期526-532,共7页Chinese Journal of Medical Genetics

基　　金：吉林省科技创新中心项目(20210502001ZP)。

摘　　要：目的对1个Rett综合征(RTT)家系进行胚胎植入前遗传学检测(PGT)。方法选取2021年6月4日于吉林大学第一医院生殖产前中心就诊的1个RTT家系为研究对象。用二代测序和Sanger测序对家系成员MECP2基因的变异情况进行分析。用直接测序检测囊胚MECP2基因c.925C>T位点的携带状态,采用Sanger测序对结果进行验证。选择MECP2基因及上下游2 Mb范围内168个有效SNP位点构建家系单体型,用于对携带该变异的胚胎进行筛选,选取未检测到变异的胚胎分析染色体非整倍体的情况。结果PGT检测显示7个囊胚中有5个未携带变异,2个携带致病性变异。结合非整倍体检测的结果,提示在5个未携带变异的囊胚中有2个为整倍体。经遗传咨询后,该夫妇选择移植最优囊胚后临床妊娠,羊水产前诊断提示胎儿染色体核型正常且未携带致病性变异,足月剖宫产术娩出一健康女婴。结论二代测序技术可实现高效的PGT检测,减少RTT在患病家系中的再发风险。Objective To carry out preimplantation genetic testing(PGT)for a Chinese pedigree affected with Rett syndrome(RTT).Methods A pedigree affected with RTT who had presented at the First Hospital of Jilin University on June 4,2021 was selected as the study subject.Variant of the MECP2 gene was analyzed by next generation sequencing(NGS)and Sanger sequencing.Direct sequencing was also used to determine the carrier status for the c.925C>T variant of the MECP2 gene in the blastocysts,and Sanger sequencing was used to validate the results.The MECP2 gene and 168 effective single nucleotide polymorphism(SNP)loci within 2 Mb ranges up-and downstream of the gene were used to construct a haplotype for analyzing the variant site in the embryos,and embryos without the variant were subjected to the analysis for chromosomal aneuploidies.Results PGT analysis revealed that five out of seven blastocysts did not harbor the pathogenic variant.The results of aneuploidy analysis indicated that two out of five blastocysts without the variant were euploid.Following genetic counselling,the couple had opted to transplant the optimal blastocyst.Following clinical pregnancy,prenatal diagnosis showed that the fetus has a normal chromosomal karyotype,and the c.925C>T variant was not detected in the amniotic fluid sample.A healthy girl was born by Cesarean section at full term.Conclusion NGS can attain efficient PGT detection and reduce the risk of disease recurrence in families affected with RTT.

关 键 词：二代测序 RETT综合征 MECP2基因 植入前遗传学检测 

分 类 号：R714.5[医药卫生—妇产科学] R394[医药卫生—临床医学]