联合应用多种分子遗传学技术阐述染色体芯片结果中潜在的结构异常  

Potential structural abnormalities in chromosome microarray results by a combination of multiple molecular genetic techniques

作　　者：唐利芳 丁焘 戴红 张庆立[2] 王环环[3] 季星[3] 叶荟[3] 倪琳[3] 曹英[3] 魏巍 孙云龙 肖冰[3] TANG Lifang;DING Tao;DAI Hong;ZHANG Qingli;WANG Huanhuan;JI Xing;YE Hui;NI Lin;CAO Ying;WEI Wei;SUN Yunlong;XIAO Bing(Xinhua Hospital Affiliatedto Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China;Department of Pediatrics;Shanghai Institute for Pediatric Research,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China)

机构地区：[1]上海交通大学医学院附属新华医院崇明分院儿内科,上海202150 [2]上海交通大学医学院附属新华医院儿内科,上海200092 [3]上海交通大学医学院附属新华医院上海市儿科医学研究所,上海200092

出　　处：《临床儿科杂志》2019年第6期440-444,共5页Journal of Clinical Pediatrics

基　　金：上海市卫计委面上项目(No.201540054)

摘　　要：目的探讨拷贝数变异中潜在的结构异常。方法通过联合应用常规核型分析及FISH等分子生物学技术对4例存在拷贝数变异的智能障碍合并多发畸形的患儿进行鉴定,明确其染色体结构异常;进而对2个家系进行产前诊断及随访。结果4例患儿经染色体芯片检测发现存在拷贝数变异,分别为16 pter缺失/19 qter重复、18 pter缺失/18 qter重复、13qter缺失和3p13-14缺失。联合核型分析及FISH检测明确患儿潜在的结构异常,分别为1例染色体末端不平衡易位der(16)(t 16 p;19 q)、1例倒位重复缺失invdup18p/del 18q、1例涉及随体易位(13 qs)及1例父源性平衡插入重组导致3 p间隙性缺失或重复。其中2例为家族性平衡重组导致,1例未确定但存在再发风险,1例为新发改变。其中2个家系于孕中期进行产前诊断,并随访证实与产前诊断结果一致。结论染色体芯片发现单纯拷贝数变异者可能存在潜在的染色体结构异常,联合应用多种技术可以明确潜在的结构异常,并提供准确的再发风险评估,从而指导疾病的产前诊断。Objective To explore the potential structural abnormalities in copy number variation.Method Four mentally retardated children with copy number variant complicated with multiple malformations were examined by combination of conventional karyotype analysis and FISH molecular biology techniques for identification of their chromosome structural abnormalities,and then prenatal diagnosis and follow-up were carried out in two families.Results Four children were found to have copy number variations by chromosome microarray detection,which were 16pter deletion/19qter duplication,18pter deletion/18qter duplication,13qter deletion and 3p13-14 deletion respectively.Potential structural abnormalities were identi fied by the combination of karyotype analysis and FISH detection:one case of chromosome end imbalance translocation der(16)t(16p;19q),one case of inverted repetitive deletion invdup18p/del 18q,one case involving a telo-satellite translocation(13qs),and one case of a parent balanced insertion recombination leading to 3p interstitial deletion or duplication.Among them,2 cases were caused by familial balanced reorganization,one case was unknown for the cause but at risk of recurrence,and one case had a new change.Prenatal diagnosis was performed in 2 families in the second trimester,and the follow-up results were consistent with the prenatal diagnosis.Conclusion Chromosome microarray can detect potential chromosomal structural abnormalities in patients with simple copy number variation.Application of multiple techniques combined can identify potential structural abnormalities and provide accurate risk assessment for recurrence,so as to achieve prenatal diagnosis of diseases.

关 键 词：拷贝数变异 染色体核型分析 染色体芯片 荧光原位杂交 

分 类 号：R725.9[医药卫生—儿科] R440[医药卫生—临床医学]