1例Y染色体结构异常嵌合体胎儿的产前诊断分析

Prenatal diagnosis of a fetus with Y-chromosome structural abnormality

目的 通过分析1例Y染色体结构异常胎儿标本的单核苷酸多态性微阵列芯片(SNP-array)、荧光原位杂交(FISH)和染色体核型分析结果,比较各种方法在产前诊断中的联用价值。方法 无创产前筛查(NIPT)提示1病例性染色体数目减少。产前诊断羊水穿刺后行快速非整倍体分子诊断、SNP-array和核型分析。3种方法结果并不完全一致,进一步行FISH检测以明确结果。结果 快速非整倍体分子检测结果提示胎儿X染色体1个信号,Y染色体2个信号。SNP-array检出结果为Yq11.221q11.23x0、Yp11.31q11.221x2,提示Y染色体长臂部分片段缺失,大小为12.54 Mb,缺失片段主要涉及生精功能AZFb+c区域。核型分析结果为mos 46,X,psu idic(Y)(q11.221)[62]/46,X,del(Y)(q11.221)[8],提示胎儿为Y染色为等臂假双着丝粒与Y长臂片段缺失嵌合体,与SNP-array所提示的断裂点位置一致。对胎儿羊水间期和中期细胞进一步FISH检测结果为(DYZ3)X1[30]/(DYZ3)X2[70],提示胎儿Y染色体结构异常嵌合。结论 对NIPT提示性染色体异常的胎儿,建议多种遗传学检测方法联用,以准确检出性染色体结构异常及排除是否存在嵌合现象,提供更准确和科学的遗传咨询。

Objective To compare the value of single nucleotide polymorphism array(SNP-array),fluorescence in situ hybridization(FISH) and karyotype analysis in prenatal diagnosis of a fetus with structural abnormality of Y chromosome.Methods A high-risk case with a reduced number of sex chromosomes is indicated by noninvasive prenatal screening(NIPT).Rapid molecular diagnosis of aneuploidy,single nucleotide polymorphism array(SNP-array) and karyotyping were conducted.Fluorescence in situ hybridization(FISH) was performed to clarify the results after the results of three methods were not completely consistent.Results The results of rapid aneuploidy molecular diagnosis suggested one X chromosome signal and the two Y chromosome signals,and the SNP-array results showed Yq11.221q11.23x0 and Yp11.31q11.221x2,suggesting that the Y chromosome was missing part of its long arm,with the size of 12.54 Mb,and the missing fragments were mainly related to the spermatogonial function of the AZFb+c region.The karyotype analysis results are:mos 46,X,psu idic(Y)(q11.221)[62]/46,X,del(Y)(q11.221)[8],indicating the fetus is a mosaic with an isodicentric Y chromosome with pseudoautosomal region and a deletion of the long arm fragment of chromosome Y,consistent with the breakpoints indicated by the SNP-array.Further FISH testing on fetal amniotic fluid interphase and metaphase cells showed:(DYZ3)X1[30]/(DYZ3)X2[70],suggesting a mosaicism with structural abnormalities of the Y chromosome in the fetus.Conclusion For fetuses with NIPT suggestive of sex chromosome abnormalities,it is recommended that multiple genetic tests be used in combination to accurately detect sex chromosome structural abnormalities and exclude the presence of chimerism,which can provide more accurate information for genetic counseling.