Cardiac-Urogenital综合征胎儿的基因变异分析  

Genetic variation analysis of fetus with Cardiac-Urogenital syndrome

作　　者：武辉艳 陈雪[1,2] 马盼盼 张庆华 郝胜菊[1,2] 周秉博 WU Huiyan;CHEN Xue;MA Panpan;ZHANG Qinghua;HAO Shengju;ZHOU Bingbo(Gansu Provincial Maternity and Child-care Hospital,Medical Genetics Center,Gansu Provincial Central Hospital,Lanzhou,Gansu 730050,China;Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases,Lanzhou,Gansu 730050,China)

机构地区：[1]甘肃省妇幼保健院/甘肃省中心医院医学遗传中心,甘肃兰州730050 [2]甘肃省出生缺陷与罕见病临床研究中心,甘肃兰州730050

出　　处：《中国优生与遗传杂志》2024年第2期336-341,共6页Chinese Journal of Birth Health & Heredity

基　　金：甘肃省科技计划资助(21JR7RA680)。

摘　　要：目的 探讨Cardiac-Urogenital综合征(CUGS)胎儿的遗传学特征,以明确病因并提供遗传咨询和生育指导。方法 选取2022年甘肃省妇幼保健院确诊的1例CUGS胎儿为研究对象。采集胎儿羊水及其父母的外周血,提取基因组DNA,进行家系全外显子测序(trio-WES)及低通量全基因组测序(CNV-seq)。应用Sanger测序技术对可疑致病突变位点进行家系验证。结果 trio-WES检测结果显示胎儿MYRF基因第25内含子存在c.3301-2A>C经典剪切变异,为自发杂合变异,父母均为野生型。该变异未检索到相关文献报道,在普通人携带频率数据库如千人基因组、gnomAD等中均未收录,为新发变异。按照美国医学遗传学与基因组学学会(ACMG)指南评估为可能致病性(likely pathogenic,PVS1+PM2_Supporting)变异。结论 基于超声结合全外显子组测序可快速、可靠地确诊CUGS患儿,为临床对胎儿的决策提供支持。同时,我们发现MYRF基因的1个新发且自发突变,国内外均未见报道,扩充了MYRF基因致病突变谱,为疾病的临床诊断和遗传咨询提供理论依据。Objective To investigate the genetic characteristics of fetuses with Cardiac-Urogenital syndrome(CUGS)in order to clarify the etiology and provide genetic counseling and fertility guidance.Methods One fetus with CUGS diagnosed in Gansu Provincial Maternity and Child-care Hospital in 2022 was selected as the study population.Fetal amniotic fluid and peripheral blood of its parents were collected,genomic DNA was extracted,and family whole exome sequencing(trio-WES) and low throughput whole genome sequencing(CNV-seq) were performed.Sanger sequencing technology was applied to perform lineage validation of suspected pathogenic mutation loci.Results trio-WES showed the presence of the c.3301-2A>C classical shear variant in intron 25 of the fetal MYRF gene,which was a de novo heterozygous variant with both parents being wild type.This variant was not retrieved from the literature and was not included in the general human carrier frequency databases such as thousand genomes,gnomAD,etc.It is a rare variant.The variant was assessed as likely pathogenic(PVS1+PM2_Supporting) according to the American College of Medical Genetics and Genomics(ACMG) guidelines.Conclusion Ultrasound-based combined with whole-exome sequencing can rapidly and reliably confirm the diagnosis of children with CUGS and support clinical decision making in fetuses.Meanwhile,we identified one novel and spontaneous mutation in MYRF gene,which has not been reported at home and abroad,expanding the spectrum of pathogenic mutations in MYRF gene and providing theoretical basis for clinical diagnosis and genetic counseling of the disease.

关 键 词：Cardiac-Urogenital综合征 MYRF基因 先心病 心脏畸形 生物信息学分析 

分 类 号：R714.5[医药卫生—妇产科学] R440[医药卫生—临床医学]