产前诊断胎儿肾脏结构异常的染色体17q12缺失综合征两例

Prenatal diagnosis of two fetuses with renal structural anomalies caused by 17q12 deletion syndrome

目的分析2例以胎儿期肾脏结构异常为主要表现的染色体17q12缺失综合征病例的产前超声特点和遗传学诊断方法。方法分析2017年在北京大学第一医院就诊的2例因孕中期B超提示胎儿肾脏结构异常孕妇的病历资料。收集胎儿染色体核型分析和基于微阵列比较基因组杂交(array-based comparative genomic hybridization, aCGH)检测,以及夫妻外周血DNA的aCGH检测等结果。结果(1)病例1中第1和第2次妊娠以及病例2的胎儿染色体核型均未见异常;病例2胎儿染色体荧光原位杂交技术检测结果未见异常。(2)病例1:第1次妊娠时,脐血DNA在染色体17q12区(34 817 422-36 168 104)存在1.351 Mb单拷贝缺失和3p26.3区(838 934-2 026 269)存在1.187 Mb单拷贝重复;孕妇外周血DNA 3p26.3区(726 645-2 026 269)存在1.299 Mb单拷贝重复。(3)病例2:脐血DNA在17q12区存在1.351 Mb单拷贝缺失,夫妻外周血DNA未检出基因拷贝数异常。结论根据孕期胎儿肾脏超声表现,通过有创性产前诊断进行基因组拷贝数变异的检测可以明确诊断并指导遗传咨询。

Objective To analyze the prenatal clinical characteristics and genetic diagnosis of two fetuses with chromosome 17q12 deletion syndrome mainly manifested by renal structural abnormalities. Methods Clinical data of two pregnant women admitted to Peking University First Hospital in 2017 due to ultrasound indication of fetal kidney structure abnormality in the second trimester were collected. Results of fetal chromosome karyotype analysis and array-based comparative genomic hybridization (aCGH), and aCGH detection of peripheral blood in the two couples were reviewed. Results (1) In both pregnancies of case 1 and case 2, no abnormal chromosome karyotype was found. In case 2, the fetal fluorescence in situ hybridization (FISH) results showed no abnormality.(2) During the first pregnancy of case 1, there was a 1.351 Mb of single-copy deletion in chromosome 17q12 (34 817 422-36 168 104) and a 1.187 Mb of single-copy duplication in chromosome 3p26.3 (838 934-2 026 269) extracted from umbilical cord blood. Moreover, a 1.299 Mb of single copy duplication in chromosome 3p26.3 (726 645-2 026 269) extracted from maternal peripheral blood was detected.(3) DNA analysis of the umbilical cord blood of case 2 showed a 1.351 Mb of single copy deletion in 17q12. No abnormal copy number variants (CNVs) were detected in the peripheral DNA of the couple. Conclusions Invasive prenatal detection of CNVs in cases with abnormal fetal kidney ultrasound findings might help to confirm the diagnosis and guide genetic counseling.