两例Y染色体部分缺失胎儿的产前诊断

Prenatal diagnosis for two fetuses carrying partial deletion of Y chromosome

目的对两例Y染色体部分缺失胎儿进行产前诊断。方法采用常规G显带及C显带技术分析胎儿及父亲的核型,采用荧光原位杂交(fluorescence in situ hybridization,FISH)、染色体拷贝数变异检测技术(copy number varaition sequencing,CNV-seq)性别决定基因(sex region of Y chromosome,SRY)检测技术及无精子因子(azoospermia factor,AZF)检测技术检测胎儿DNAO结果2例胎儿羊水染色体在320〜400条带水平均提示46,XN,del(Y)(qll.2),Y染色体着丝粒探针FISH检测结果均提示Y染色体数目未见异常。2例胎儿父亲外周血染色体核型均未见明显异常。胎儿羊水DNA拷贝数检测提示一例胎儿Y染色体q 11.221-ql2处缺失12.88 Mb,涉及全部AZFb+AZFc区域;另一例胎儿Y染色体qll.21-ql2处缺失14.84 Mb,涉及全部AZF区域。2例胎儿羊水SRY基因检测提示SRY基因阳性,SKY基因编码区未检测到已报道的致病点突变。2例胎儿基因检测提示存在AZF部分或全部缺失。结论联合多种技术有助于明确诊断Y染色体结构异常。CNV-seq检测有利于快速筛查胎儿Y染色体微缺失,可做为对染色体核型分析的补充和验证的方法。

Objective To perform prenatal diagosis for two fetuses carrying partial deletion of Y chromosome.Methods Routine G-and C-banding were carried out to analyze the chromosomal karyotypes of the fetuses and their fathers.Fetal DNA was also subjected to low-coverage massively parallel copy number variation sequencing(CNV-seq)♦fluorescence in situ hybridization(FISH),SRY gene and AZF factor testing.Results Both fetuses showed a 46,XN,del(Y)(q11.2)karyotype at 320-400 band level by the analysis of amniotic fluid chromosomes.FISH with Y chromosome centromere probe indicated that in both cases the number of Y chromosome was normal.Both fathers had an apparently normal karyotype at 320-400 band level.For fetus 1,CNV-seq test revealed a 12.88 Mb deletion at Yq11.221-q12,which encompassed the whole of AZFb+AZFc regions and may lead to male infertility,sperm deficiency and/or severe oligospermia.In fetus 2,CNV-seq also detected a 14.84 Mb deletion at Yq11.21-q12,which encompassed the whole of the AZF region and may lead to severe spermatogenesis disorder resulting in severe oligoasthenospermia and azoospermia.In both cases,testing of SRY gene was positive.No point mutation of the SRY gene was identified.Analysis of amniotic fluid DNA confirmed partial or total absence of AZF in the two fetuses,respectively.Conclusion Combined use of various technologies can enable accurate detection of structural abnormal让ies of the Y chromosome and facilitate genetic counseling.CNVseq can help with rapid screening of Y chromosome microdeletions and may be used as a complementary test for chromosomal karyotyping.