应用单核苷酸多态性-微阵列比较基因组杂交技术检测胎儿标记染色体

Prenatal diagnosis of two fetuses with de novo small supernumerary markers by single nucleotide polymorphism array based comparative genomic hybridization

目的探讨单核苷酸多态性一微阵列比较基因组杂交技术（single nucleotide polymorphism array-based comparative genomic hybridization，SNP-arrayCGH）检测胎儿标记染色体及其在产前遗传学诊断中的应用。方法应用SNP-arrayCGH技术对羊水G显带诊断出的两例携带标记染色体的胎儿（其中胎儿1核型为嵌合体47，XX，＋marl[23]／46，XX[16]、胎儿2核型为47，XX，＋nlar），进行全基因组高分辨率扫描分析，确定标记染色体来源与片段大小；并用染色体末端探针多重连接依赖探针扩增技术（multiplex ligation-dependentprobe amplification，MI．PA）对胎儿2基因组不平衡进行验证。两例胎儿超声均无明显结构异常；两例胎儿的双亲核型均正常。结果SNP-arrayCGH结果显示胎儿1标记染色体来源于9p21．1-p21．3（长度为8．3Mb），显示嵌合型，根据文献推测此区带的重复携带者可以是表型正常（或有轻微异常）的个体。胎儿2标记染色体来源于15q11．2-q13．3（长度为10．8Mb），染色体末端探针MLPA检测结果也证实了该重复的存在，此区域基因重复主要引起神经行为方面的异常。告知孕妇及家属风险，均选择终止妊娠。结论SNP-arrayCGH技术能比其他技术更精确的确定标记染色体来源，可明确标记染色体的基因型，而且能检测出嵌合型的标记染色体，适用于产前遗传学诊断，并可为产前遗传咨询提供帮助。

Objective To explore the origins of small de novo mosaic supernumerary marker chromosomes （mars） in two fetuses, and to assess the feasibility of single nucleotide polymorphism array- based comparative genomic hybridization （SNP-array CGH） for prenatal molecular cytogenetic diagnosis. Methods Two fetuses with de novo were identified. SNP-array marker chromosomes was applied to define the location and range of marker chromosomes. The karyotype of fetus I was determined to be 47, XX,＋ mar[23]/46, XX [16], and that of fetus II was 47, XX, ＋ mar. Multiplex ligation-dependent probe amplification （MLPA） was applied to verify the genomic imbalance found in fetus II. The karyotypes of parents were normal in both families. Results SNP-array CGH has indicated a 8. 3 Mb duplication at 9p21. l-p21.3 in fetus I , and a 10. 8 Mb duplication at 15q11. 2-q13. 3 in fetus II. MLPA has also confirmed a 15q terminal duplication in fetus II. Conclusion Above cases have illustrated that SNP-array CGH is a rapid, powerful and sensitive technique which may be used for identify the origins of marker chromosomes in prenatal diagnosis.