摘要
目的分析1例胎儿生长受限、长骨短、头围偏小及双肾回声增强胎儿的遗传学病因,探讨NIPBL基因无义突变的临床意义。方法收集胎儿及其父母的临床资料,通过羊水染色体核型分析、人类基因组拷贝数变异检测(CNV-seq)、全外显子组测序(WES)及Sanger测序验证NIPBL基因的变异位点。检索中国知网、万方数据、万方医学、Pubmed等数据库,并进一步分析患儿的临床症状及基因突变位点。结果测序结果提示胎儿NIPBL基因21号外显子存在c.4555A>T杂合变异,其父母未检测到相同的变异。上述变异在人类外显子数据库(ExAC)、参考人群千人基因组(1000G)和人群基因组突变频率数据库(gnomAD)等中均未见收录,综合判断为有害变异。结论NIPBL基因c.4555A>T(p.Lys1519*)无义变异的检出为该家系的产前诊断及家庭生育提供了实验依据。
Objective To analyze the genetic etiology of a fetus with growth restriction,short long bones,small head circumference and enhanced kidney echoes,and explore the clinical significance of nonsense mutations in the NIPBL gene.Methods The clinical data of the fetus and his/her parents were collected.The variation sites of the NIPBL gene were verified by the chromosome karyotype analysis of amniotic fluid,copy number variation detection in the human genome(CNV-seq),whole exome sequencing(WES)and Sanger sequencing.The databases such as China National Knowledge Infrastructure(CNKI),Wanfang Data,Wanfang Medical,and Pubmed were searched to further analyze the relationship between clinical symptoms and gene mutation sites in the fetus.Results The sequencing results showed that there was c.4555A>T heterozygous mutation in exon 21 of the NIPBL gene in the fetus,and that the same mutation was not detected in his/her parents.The above variation had not been included in databases such as Human Exon Database(ExAC),1000 genomes(1000G)and Genome Aggregation Database(gnomAD),and were comprehensively judged as harmful variation.Conclusion The detection of the nonsense variation,c.4555A>T(p.Lys1519*),in the NIPBL gene may provide experimental evidence for the prenatal diagnosis and fertility in this family.
作者
郭婷婷
常梓殷
娄欢
杨新梦
归婧
杨小风
GUO Tingting;CHANG Ziyin;LOU Huan;YANG Xinmeng;GUI Jing;YANG Xiaofeng(Department of Obstetrics and Gynaecology,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450007,Henan,China)
出处
《临床检验杂志》
CAS
2024年第9期702-706,共5页
Chinese Journal of Clinical Laboratory Science
