一例46,XN,del(11)(q14q22)胎儿的产前诊断及遗传学分析

Prenatal diagnosis and genetic analysis of a 46,XN,del(11)(q14q22)fetus

目的:联合应用无创产前检测(non-invasive prenatal testing,NIPT)、染色体核型分析和全基因组测序(whole genome sequencing,WGS)诊断1例46,XN,del(11)(q14q22)胎儿,并对其亲代进行染色体检查和家系分析,为遗传咨询提供依据。方法:抽取孕妇静脉血样进行NIPT检测;抽取孕妇静脉血样、脐血样以及男方静脉血样进行染色体核型分析和WGS检测。结果:NIPT提示胎儿存在11号染色体部分缺失。脐血染色体因分辨率低未发现异常。脐血WGS检测结果为46,XN,del(11q14.3q22.1).seq[GRCh37/hg19](90623404-97469319)×1,6.85 Mb,最终诊断胎儿核型为46,XN,del(11)(q14q22),孕妇为46,XX,del(11)(q14q22)[8]/46,XX[92],其丈夫为46,XY。夫妇两人WGS检测均未发现del(11)(q14.3q22.1)。结论:胎儿的del(11)(q14q22)来源于孕妇的低比例嵌合体。综合应用NIPT、染色体核型分析、WGS等技术能够准确诊断染色体病,减少误诊和漏诊。

Objective To diagnose a 46,XN,del(11)(q14q22)fetus by non-invasive prenatal testing(NIPT),karyotype analysis and whole genome sequencing(WGS).Methods Peripheral blood sample of the gravida was taken for NIPT screening.Blood samples of the gravida,her husband,and umbilical cord blood were also taken for chromosome karyotyping and whole genome sequencing(WGS).Results NIPT screening indicated the fetus has carried partial deletion of chromosome 11,while no chromosomal abnormality was found with the cord blood sample due to the low resolution of G-banding analysis.WGS analysis of the cord blood indicated 46,XN,del(11q14.3q22.1).seq[GRCh37/hg19](90623404-97469319)×1,6.85 Mb.The karyotype of the fetus was eventually determined as 46,XN,del(11)(q14q22).Karyotyping analysis suggested that the gravida and her husband were 46,XX,del(11)(q14q22)[8]/46,XX[92]and 46,XY,respectively.However,neither of them was found to harbor the del(11)(q14q22)by WGS.Conclusion The abnormal karyotype of the fetus has derived from its mother’s low percentage mosaicism.Combined NIPT,karyotyping analysis and WGS can detect chromosomal disorders with accuracy.