上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（临床研究） • 上一篇    下一篇

靶向基因高通量测序技术诊断儿童基因组病的可行性研究

张欢欢1,2， 李牛1， 郁婷婷1， 姚如恩1， 卿艳荣1， 王秀敏1,3， 沈亦平1,4， 王剑1   

  1. 1.上海交通大学 医学院附属上海儿童医学中心  医学遗传科（分子诊断实验室）， 上海 200127； 2.上海市同仁医院检验科， 上海 200336； 3.上海交通大学 医学院附属上海儿童医学中心  内分泌遗传代谢科， 上海 200127； 4.美国哈佛大学 医学院附属波士顿儿童医院基因诊断实验室， 波士顿 02115
  • 出版日期:2016-09-28 发布日期:2016-10-31
  • 通讯作者: 王剑， 电子信箱： wangjian@scmc.com.cn。
  • 作者简介: 张欢欢（1983—），女，主管技师，硕士生；电子信箱：zhh743@126.com。
  • 基金资助:

    国家自然科学基金（81201353，81371903，81472051）；上海市科委国际合作项目（15410722800）；上海市教育委员会高峰高原学科建设计划（20152529）

Feasibility study of the targeted next-generation sequencing technology in the diagnosis of childrens genomic disease

ZHANG Huan-huan1,2, LI Niu1, YU Ting-ting1, YAO Ru-en1, QING Yan-rong1, WANG Xiu-min1,3, SHEN Yi-ping1,4, WANG Jian1   

  1. 1.Department of Medical Genetics (Molecular Diagnostic Laboratory), Shanghai Childrens Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China;  2.Department of Clinical Laboratory, Tongren Hospital, Shanghai 200336, China; 3. Department of Endocrine and Genetic Metabolic, Shanghai Childrens Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; 4.Department of Gene Diagnostic Laboratory, Boston Childrens Hospital, Harvard Medical School, Boston 02115, USA

  • Online:2016-09-28 Published:2016-10-31
  • Supported by:

    National Natural Science Foundation of China, 81201353， 81371903， 81472051; Project of Science and Technology Commission of Shanghai Municipality, 15410722800; Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support， 20152529

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摘要：

目的·对10例临床怀疑基因组病的患儿进行临床分子诊断，初步探讨靶向基因高通量测序技术检测拷贝数变异(CNVs)的可行性。方法·对患儿进行外周血DNA靶向高通量测序，通过生物信息学分别分析其基因组CNVs，确定致病CNVs位点及大小，同时使用染色体基因芯片技术作为对照方法检测CNVs。结果·靶向测序分析结果表明：在其中1个患儿基因组的17号染色体q25.1—q25.3区域存在9 345 kb的重复（3个拷贝），而另1个患儿基因组中存在15号染色体q11.2—q13.1区域的8 232 kb的杂合缺失，其余8例患儿基因组未见可疑CNVs。染色体基因芯片检测结果与高通量测序结果相比高度一致。 结论·借助于分子诊断技术，2名患儿被确诊为基因组病。临床应用靶向基因高通量测序技术检测CNVs完全具有可行性。

关键词: 拷贝数变异, 基因组病, 高通量测序, 染色体基因芯片

Abstract:

Objective·To perform clinical molecular diagnosis for 10 Chinese children with highly-suspected genomic disorders and to evaluate the feasibility of next generation sequencing (NGS) with target capture library in decteting copy number variants (CNVs). Methods·All the patients were evaluated by NGS with SureSelect Inherited Diseases library. The location and size of pathogenic CNVs were identified through bioinformatics analysis. Meanwhile, chromosome microarray analysis (CMA) was used to verify these CNVs. Results·NGS results showed that a 9 345 kb duplication (3 copies) in 17q25.1—q25.3 was detected in chromosome 17 of case 1 and a 8 232 kb heterozygous deletion in 15q11.2—q13.1 was detected in chromosome 15 of case 2. No suspicious CNVs were identified in other 8 cases. The CMA testing results were highly consistent with those of NGS. Conclusion·Two patients were diagnosed with genomic disorders by molecular diagnosis approach. Our research indicates that targeted NGS technique is quite feasible for CNV detection.

Key words: copy number variations, genomic disorders, next generation sequencing, chromosome microarray analysis