摘要
目的通过全基因组测序(WGS)对1例拷贝数变异测序(CNV-seq)提示为Xq28重复的可能致病性变异进行重新分析, 为产前遗传咨询提供依据。方法以2023年5月中国医科大学附属盛京医院羊水CNV-seq检测发现的1例Xq28重复胎儿的父亲作为研究对象。对其进行WGS检测, 并用生物信息学软件对其染色体结构和拷贝数进行分析, 并用定量PCR检测其MECP2基因表达的变化。本研究通过了中国医科大学附属盛京医院伦理委员会的审查(批准号:2013PS33K)。结果胎儿父亲X染色体存在ChrX:153302641153503563重复和4个断点。通过对其重复区域及断点进行分析, 发现该重复区涉及MECP2基因第1 ~ 3外显子以及5′UTR的部分序列, 且插入到了X染色体的p11区, 同时, Xp11区内与重复区段相连接的部分序列还存在倒位。RT-PCR检测显示MECP2基因的mRNA表达水平正常。Xq28区片段重复未涉及整个MECP2基因, 未破坏其结构或影响其表达。结论 WGS能够为染色体变异提供更精确的诊断, 为患儿家系的遗传咨询提供依据。
Objective To re-analyze a likely pathogenic variant in the Xq28 region identified by copy number variation sequencing(CNV-seq)through whole genome sequencing(WGS).Methods A fetus found to harbor a duplication in the Xq28 region by CNV-seq at Shengjing Hospital Affiliated to China Medical University in May 2023 was selected as the study subject.WGS was carried out for the fetus and its father.Bioinformatic software was used to analyze the chromosomal structure and CNVs.Quantitative PCR(qPCR)was applied to determine the expression level of the MECP2 gene.This study has been approved by the Ethics Committee of Shengjing Hospital(Ethic No.2013PS33K).Results A duplication(ChrX:153302641_153503563)and four breakpoints were identified on the X chromosome of the fetus'father.Bioinformatic analysis revealed that the duplicated region has involved exons 1 to 3 and part of the 5'-UTR of the MECP2 gene,which was inserted into the Xpll region.Additionally,an inversion was detected in the Xpl1 region adjacent to the duplicated segment.RT-PCR results showed normal level of MECP2 mRNA expression.The Xq28 duplication has not encompassed the entire MECP2 gene,nor disrupted its structure or altered its expression.Conclusion WGS has enabled more precise diagnosis of chromosomal structural variants and provided guidance for accurate genetic counseling for the affected families.
作者
杨昱来
李闯
高铭
吕远
Yang Yulai;Li Chuang;Gao Ming;Lyu Yuan(The First Clinical School of China Medial University,Shenyang,Liaoning 110001,China;Department of Gynecology and Obstetrics,Shengjing Hospital Affiliated to China Medical University,Key Laboratory of Maternal-Fetal Medicine of Liaoning Province,Shenyang,Liaoning 110004,China;Prenatal Diagnosis Center,Shenyang women's and Children's Hospital,Shenyang,Liaoning 110011,China)
出处
《中华医学遗传学杂志》
2025年第3期355-359,共5页
Chinese Journal of Medical Genetics
基金
沈阳市科技计划(22-321-33-21)。
