摘要
目的明确一例智力低下、无语言能力和肌张力低下的先证者遗传学病因,并对孕妇行产前基因诊断,以期避免智力低下患儿出生。方法回顾收集先证者的临床病例资料,采用全外显子测序(WES)技术对先证者进行基因检测,使用Sanger测序技术对先证者及其父母进行候选基因位点验证,并通过羊水穿刺对孕妇进行产前诊断和遗传咨询。结果CHD8基因c.3293del(p.P1098Hfs*12)杂合变异是先证者的致病原因,高危胎儿携带CERT1基因c.1708A>G(p.Arg570Gly)杂合变异,经充分遗传咨询后,孕妇选择继续妊娠,目前仍在随访中。结论WES发现先证者携带CHD8基因c.3293del(p.P1098Hfs*12)杂合变异,父母均为野生型,先证者为新发突变。对孕妇羊水样本进行检测,胎儿未携带CHD8基因c.3293del杂合变异,但检测出一个临床意义不明的CERT1基因c.1708A>G(p.Arg570Gly)杂合变异,父母均为野生型。查阅文献并行生物信息学分析发现该变异可能是良性变异。
Objective To identify the genetic etiology of mental retardation,speechlessness and hypotonia in a proband,and to perform prenatal genetic diagnosis on the pregnant woman in order to avoid the birth of child with mental retardation.Methods The clinical case data of the proband were retrospectively collected,the gene detection of the proband was performed by whole exome sequencing(WES)technology,the candidate gene loci of the proband and her parents were verified by Sanger sequencing technology,and the prenatal diagnosis and genetic counseling of the pregnant woman were performed by amniocentesis.Results The heterozygous variant c.3293del(p.P1098Hfs*12)in the CHD8 gene was the cause of the proband,the high-risk fetus carried the heterozygous variant c.1708A>G(p.Arg570Gly)in the CERT1 gene,and after adequate genetic counseling,the pregnant woman chose to continue the pregnancy and is still under follow-up.Conclusion WES finds that the proband carries the heterozygous variant c.3293del(p.P1098Hfs*12)in the CHD8 gene,both parents are wild-type,and the proband is a new mutation.In the amniotic fluid sample of the pregnant woman,the fetus does not carry the heterozygous variant c.3293del in the CHD8 gene,but a heterozygous variant c.1708A>G(p.Arg570Gly)in the CERT1 gene of unknown clinical significance is detected,and both parents are wild-type.Literature review and bioinformatics analysis find that the variant may be benign.
作者
常媛媛
张颖
徐盈
石润茜
张建芳
张媛媛
CHANG Yuanyuan;ZHANG Ying;XU Ying;SHI Runqian;ZHANG Jianfang;ZHANG Yuanyuan(Medical School of Yan'an University,Yan'an 716099,China;Department of Obstetrics and Gynecology,Xijing Hospital,Air Force Medical University,Xi'an 710032,China;Xijing 986 Hospital,Xi'an 710054,China;Department of Obstetrics and Gynecology,Yan'an University Affiliated Hospital,Yan'an 716099,China)
出处
《空军军医大学学报》
CAS
2024年第6期645-649,共5页
Journal of Air Force Medical University
基金
陕西省自然科学基础研究计划项目(2022JQ-977)。
