两例父源性17q12微缺失综合征胎儿的产前诊断和遗传学分析

目的探讨两例父源性17q12微缺失综合征胎儿的产前诊断和遗传咨询。方法一名孕妇的两例胎儿的孕中晚期超声检查均提示肾脏异常和羊水过多,应用单核苷酸多态性分析(single nucleotide polymorphism array,SNP-array)分别对第1胎的脐血样本和第2胎的羊水样本进行产前诊断。发现第1胎染色体17q12微缺失后,父母进行外周血SNP-array检测以确定遗传来源。结合双亲临床病史,其父亲进行泌尿系统相关的565个基因的高通量测序,以排除泌尿系统及生殖器官先天性结构畸形相关的已知致病变异或疑似致病变异可能。结果该家系两例胎儿SNP-array结果均为arrhg19]17q12(34822465~36243365)×1,大小约1.4 Mb,为17q12微缺失综合征,遗传自父亲。胎儿父亲未发现泌尿系统相关的致病或疑似致病变异。结论父源性17q12微缺失可能为两例胎儿超声肾脏异常和羊水过多的遗传学病因。产前SNP-array检测可明确诊断,为该家系的遗传咨询及产前诊断提供依据。

Prenatal diagnosis and genetic analysis of two fetuses with paternally derived 17q12 microdeletions

Objective To reported on two fetuses diagnosed with 17q12 microdeletion syndrome.Methods The two fetuses were respectively found to have renal abnormalities and polyhydramnios upon second and third trimester ultrasonography.Umbilical cord blood of the first fetus and amniotic fluid of the second fetus were subjected to single nucleotide polymorphism array(SNP-array)analysis.After 17q12 microdeletion was found in the first fetus,SNP-array detected the peripheral blood of the parents to determine the genetic source.Combined with medical history of the parents,the father underwent high-throughput sequencing of 565 urinary system-related genes to exclude the pathogenic or likely pathogenic variants associated with congenital structural malformations of the urinary and reproductive organs.Results In both fetuses,SNP-array has revealed a 1.42 Mb deletion at 17q12,or arrhg19]17q12(34822465-36243365)×1.In both cases the microdeletion was inherited from the father,in whom no urinary disease-related pathogenic or likely pathogenic variants was identified.Conclusion Paternally derived 17q12 microdeletions probably underlay the genetic etiology of the two fetuses with renal ultrasound abnormalities and polyhydramnios.SNP-array can enable the diagnosis and facilitate genetic counseling and prenatal diagnosis for the families.