一例手足裂胎儿的临床特征及病因学分析

Clinical feature and pathogenic analysis of a fetus with split hand-foot malformation

目的分析一例手足裂胎儿的临床特征以及基因组拷贝数变异(copy number variations,CNVs)的情况。方法收集孕期胎儿超声以及引产儿X线检查资料并进行总结。应用二代测序(next generation sequencing,NGS)检测引产儿的CNVs。用NGS及荧光原位杂交(fluorescence in situ hybridization,FISH)对其亲代进行分析,用实时荧光定量PCR对胎儿染色体异常区域的基因表达量进行检测。结果超声及X线检查提示胎儿右手及双足均呈"V"形开裂。NGS检测提示胎儿染色体7q21.3区存在约0.36 Mb的缺失。NGS及FISH检测提示其双亲均未携带相同的变异。实时荧光定量PCR结果提示胎儿DYNC1I1基因存在杂合缺失,而SEM1、DLX5、DLX6基因的拷贝数则未见异常。结论胎儿手足裂畸形的致病原因为7q21.3区微缺失,后者为新发变异。

Objective To analyze the clinical feature of a fetus with split hand-foot malformation(SHFM)and to explore its etiology.Methods Ultrasonographic finding of the fetus and X-ray examination of the abortus were reviewed.Genomic copy number variations(CNVs)of the fetus was analyzed by next-generation sequencing(NGS).Its parents were subjected to chromosomal karyotyping,NGS and fluorescence in situ hybridization(FISH)assays.Real-time fluorescence quantitative PCR was used to measure the expression of genes from the region containing abnormal CNVs.Results Ultrasonography and X-ray revealed that the right hand and both feet of the fetus were in a"V"shape,which was suggestive of SFHM.The results of NGS revealed that the fetus has carried a 0.36 Mb deletion at 7q21.3 region.FISH and NGS analysis of both parents were normal.Real-time fluorescence quantitative PCR confirmed that the fetus carried a single copy of DYNC1I1 gene,while the copy numbers of SEM1,DLX5 and DLX6 genes were normal.Conclusion The 7q21.3 microdeletion probably underlies the SHFM of the fetus,which has a de novo origin.