微阵列比较基因组杂交技术检测先天性心脏畸形胎儿的隐藏基因组拷贝数变异

目的 检测1例先天性主动脉弓离断和室间隔缺损胎儿的基因组拷贝数变异(copy number variations,CNVs),寻找其致病的遗传学证据,探讨微阵列比较基因组杂交技术(array-based comparative genomic hybridization,array-CGH)在分子细胞遗传诊断中应用的可行性.方法 对该患儿脐血及其父母外周血进行常规G显带核型分析,发现胎儿核型为46,XX,t(7;9)(q12;q21),双亲核型正常.进而应用array-CGH芯片对患儿进行全基因组高分辨率扫描分析,采用荧光原位杂交技术(fluorescence in situ hybridization,FISH)对新发现的CNVs进行实验验证.结果 array-CGH分析发现胎儿基因组存在1个病理性亚显微结构的拷贝数变异:del(22)(q11.2)(17 370 128～19 790 009,2.42 Mb).FISH实验结果验证了此22q11.2微缺失的存在.结论 隐藏的22q11.2微缺失可能是此胎儿致病的原因;染色体平衡易位的先天缺陷胎儿可能会含有位于重排断裂点区域之外的亚显微结构基因组拷贝数变异;微阵列比较基因组杂交具有高分辨率、高通量和高准确性等优点,适用于亚显微基因组拷贝数变异的检测.

Detection of cryptic copy number variations in a fetus with congenital heart disease by array-based comparative genomic hybridization

Objective To detect the copy number variation (CNV) of a fetus with interrupted aortic arch and ventricular septal defect, in order to explore the underlying genetic causes of the congenital malformation, and investigate the feasibility of array-based comparative genomic hybridization (array-CGH)in molecular cytogenetic diagnosis. Methods The whole genome of the fetus with de novo apparently balanced translocations [46, XX, t ( 7 ; 9 ) ( q12 ; q21 ) ] diagnosed by G-banding was scanned and analyzed by array-CGH, and the copy number variation was confirmed by fluorescence in situ hybridization (FISH).Results A pathologic submicroscopic CNV ldel(22) (q11. 2) (17 370 128-19 790 009,-2. 42 Mb)] was identified and mapped by array-CGH. FISH test confirmed the microdeletion detected by array-CGH.Conclusion The cryptic 22q11.2 deletion might be the reason leading to the congenital malformation of the fetus. This study provides evidence that apparently balanced translocations classified by conventional cytogenetic techniques may host additional submicroscopic CNVs which are not located at the breakpoints.Due to the high-resolution, high-throughput and high-accuracy, array-CGH is considered to be a powerful tool for submicroscopic CNVs detection.