多技术联合检测产前4q末端缺失胎儿一例

Combined multi-technique testing of a fetus with a prenatal 4q terminal deletion

目的对一例无创产前DNA检测(NIPT)提示4q末端缺失高风险孕妇进行介入性产前诊断(IPD),分析其拷贝数变异区域所包含的基因,明确该区域的断裂点,并探讨其可能的基因型-表型相关性。方法常规G显带技术对胎儿羊水细胞及其父母和哥哥的外周血淋巴细胞行染色体核型分析,利用染色体微阵列分析(CMA)技术对异常核型样本进行全基因组拷贝数变异分析。结果胎儿哥哥和父亲的外周血常规染色体核型分析未见异常,母亲的外周血常规染色体核型分析结果显示为46,XX,del(4)(q35.1),胎儿羊水细胞的4号染色体出现与母亲相同的变异。CMA分析结果显示,胎儿及其母亲均有4号染色体长臂末端部分缺失,缺失区域为4q35.1q35.2(186431008190957460),片段大小约4.5 Mb,涉及SORBS2、TLR3、CYP4V2等38个OMIM基因。父亲CMA结果未见异常。结论本病例和文献综述表明,对于4号染色体长臂末端缺失的表型变异较大的综合征需要进行更详细的基因分析,来明确遗传学机制,以便建立更精确的基因型-表型相关性。

Objective To carry out interventional prenatal diagnosis(IPD)to a case of chromosome 4 q terminal deletion high-risk by noninvasive prenatal test(NIPT).What genes were included in the copy number variation(CNV)region and its break site would be analysis.And we would review its possible genotype-phenotype correlation about this CNV.Methods Chromosome karyotype analysis was performed on the amniotic fluid cells and the peripheral blood lymphocytes of fetal’s parents and brother by conventional G-banding technique.And then,the DNA of abnormal karyotype samples were detected by chromosomal microarray analysis(CMA)in order to analysis the wide-genome copy numbers variation(CNV).Results The results about karyotype analysis of the fetal’s brother and father showed no abnormalities.The mother’s karyotype was 46,XX,del(4)(q35.1).The chromosome 4 of the amniotic fluid cell was the same as that of the mother.The results of CMA analysis showed that both the fetus and his mother had a partial deletion of 4 q terminal.The deletion region was 4 q35.1 q35.2(186431008190957460),and size of the CNV was about 4.5 Mb,which involving 38 OMIM genes such as SORBS2,TLR3,CYP4 V2,et al.Father’s CMA result showed no abnormalities.Conclusion This case and some reviews indicate that the phenotype lead by 4 q terminal deletion is very variable.In order to establish more precise genotypic-phenotypic correlations,more detailed genetic analysis is needed to clarify the genetic mechanisms.