微阵列比较基因组杂交技术在出生缺陷新生儿中的应用研究

Application of array-based comparative genomic hybridization in newborns with birth defects

目的:探讨微阵列比较基因组杂交技术在出生缺陷新生儿中的应用价值。方法:选取不明原因的出生缺陷新生儿20例为研究对象,采用微阵列比较基因组杂交技术评估出生缺陷发生的遗传病因。结果:20例患儿经常规染色体检测存在2例(10%)染色体拷贝数变异,但无法明确病因。另经微阵列比较基因组杂交技术检测后,有5例患儿(25%)存在染色体拷贝数变异,4例患儿明确病因,与常规染色体检测结果比较,差异有统计学意义(P<0.05)。其中,1号患儿在chr22q13.31q13.33区域发生3.8 Mb片段缺失,为Phelan-McDermid综合征;2号患儿在chr15q11.2q13.1区域发生约6.2 Mb片段缺失,与Prader-Willi综合征相关;3号患儿在chr11q24.2q25区域发生10.3 Mb片段缺失,为Jacobsen综合征;4号患儿在chr5q32处存在约311 Kb缺失片段,该片段缺失可致Treacher Collins综合征;5号患儿多条染色体发生了大片段纯合子(>3Mb)现象,片段长度总和大约为171.0 Mb,占常染色体基因组片段总长度的6.0%,无明确临床意义。其余患儿染色体拷贝数为正常多态性改变。结论:在常规染色体检测无法确诊的情况下,采用微阵列比较基因组杂交技术进行全基因组的快速扫描可明确部分患儿病因,具有重要的临床意义。

Objective:To explore the application value of array-based comparative genomic hybridization in newborns with birth defects.Methods:20 newborns with unexplained birth defects were selected as research objects.The genetic etiology of birth defects in children was assessed by array-based comparative genomic hybridization.Results:Chromosome copy number variation was found in 2(10%)of 20 children by routine chromosome testing,but the cause was not clear.In addition,5 children(25%)had chromosome copy number variation and 4 children had clear etiology after array-based comparative genomic hybridization,the results were significantly different from those of conventional chromosome detection(P<0.05).Among them,patient 1 had a 3.8Mb fragment deletion in chr22q13.31q13.33 region,which was Phelan-McDermid syndrome.Patient 2 had about 6.2Mb fragment deletion occurred in chr15q11.2q13.1,which was related to Prader-Willi syndrome.Patient 3 had 10.3Mb missing in chr11q24.2q25 region,which was Jacobsen syndrome.Patient 4 had about 311Kb missing fragments in chr5q32,which might cause Treacher Collins syndrome.Large fragment homozygous(>3Mb)phenomenon occurred in multiple chromosomes of patient 5,the total fragment length was about 171.0Mb,accounting for 6.0%of the total length of autosomal genome segments,with no clear clinical significance.Conclusion:In the case that conventional chromosome detection cannot be confirmed,the rapid scanning of whole genome by array-based comparative genomic hybridization technique can identify the etiology of some children,which has important clinical significance.