微阵列比较基因组杂交检测复杂染色体重排胎儿隐藏的基因组拷贝数变化

Array-based comparative genomic hybridization detection of cryptic copy number variations in a fetus with de novo complex chromosome rearrangement

目的:检测复杂染色体重排断裂点区域是否隐藏有亚显微拷贝数变化,确定重排的复杂性,探讨微阵列比较基因组杂交在分子细胞遗传诊断中运用的可行性和优越性.方法:应用微阵列比较基因组杂交芯片对一被传统G显带和多色荧光原位杂交诊断为平衡复杂染色体重排(46,XX.t(4;5;15)(4pter→4q23::15q23→15qter;4qter→4q23::5p15→5qter;15pter→15q23::)dn)的胎儿进行全基因组高分辨率扫描和分析.结果:微阵列比较基因组杂交显示胎儿存在3个亚显微拷贝数变化:dup(5)(q13.2)(69274233-70622915,～1.35Mb),del(15)(q11.2)(18657188-20080135,～1.42Mb)和del(18)(p11.31-p11.23)(7069849-7567290,～0.49Mb),均定位于重排断裂点(4q23,5p15和15p23)以外的区域,与断裂点不相关.结论:被传统细胞遗传分析技术诊断为平衡染色体重排的病例会隐藏有亚显微拷贝数变化,且这些拷贝数变化并非一定定位于重排断裂点区域;对于检测和定位亚显微拷贝数变化,微阵列比较基因组杂交是一个非常强大和有效的工具.

AIM：To detect whether the breakpoint regions of a complex chromosomal rearrangement（CCR）host cryptic submicroscopic copy number variations（CNVs）,ascertain the complexity of the rearrangement,and investigate possibility and superiority of array-basedcomparative genomic hybridization（array-CGH）in molecular cytogenetic diagnosis.METHODS：The whole genome of a fetus with de novo apparently balanced CCR[46,XX,t（4;5;15）（4pter→4q23：：15q23→15qter;4qter→4q23：：5p15→5qter;15pter→15q23：：）dn] diagnosed by G-banding and multicolour fluorescence in situ hybridization was scanned and analysed by array-CGH.RESULTS：Three submicroscopic CNVs,dup（5）（q13.2）（69274233-70622915,-1.35 Mb）,del（15）（q11.2）（18657188-20080135,-1.42 Mb）and del（18）（p11.31-p11.23）（7069849-7567290,-0.49 Mb）were identified and mapped.All the CNVs locate outside the breakpoints,none of which is associated with translocation breakpoint regions.CONCLUSION：This study provides evidence that apparently balanced CCRs classified by conventional cytogenetic techniques may host additional chromosomal imbalances which are not always located at the breakpoints,and array-CGH is a useful tool for detectingand mapping cryptic submicroscopic imbalances.