杜氏肌营养不良（DMD）是最常见的致死性肌肉疾病，致病基因DMD位于Xp21.2，全长2.4Mb，突变类型多，外显子缺失/重复突变约占70%,散发病人新发突变占1/3。该病无有效治疗方法，建立无创产前诊断已成为亟待解决的热点问题。本原理论证研究针对遗传和新发DMD基因外显子缺失和重复突变胎儿，用孕妇外周血浆游离DNA为研究材料，通过目标区域捕获和新一代测序技术，进行外显子捕获和高通量测序，比较胎儿外显子缺失/重复组与对照组间目标外显子数据的差异，完成胎儿和孕妇DMD的遗传状态分析，研究不同数据分析方法，建立遗传性和新发性胎儿DMD基因缺失/重复型突变无创产前诊断新方法。实现存在/不存在孕妇DMD基因外显子杂合性缺失/重复突变背景下，检测胎儿DMD基因外显子178bp缺失/重复，该方法可应用于其他携带小片段外显子缺失/重复突变基因的无创产前诊断，不同以往技术仅限于检测胎儿性别或染色体异倍体。

Duchenne muscular dystrophy (DMD) is the most frequent and lethal form of muscular dystrophy. The causative gene DMD is located at Xp21.1 and covers a large genomic size of 2.4Mb, in which many types of mutations involve, however, exon deletions/duplications are found in about 70% of all patients. De novo mutations account for 1/3 of all sporadic patients. Noninvasive prenatal diagnosis for DMD has been a hot issue to be solved in recent years. This proof-of-principle study aims to determine the mutational status of exon deletions/duplications in the DMD fetus from maternal plasma.Targeted exon capture and deep sequencing will be performed on cell-free DNA fragments extracted from maternal plasma using next generation sequencing technology.Comparative analysis of the differences of targeted exon sequencing data between the exon deletions/duplications group and the control will be used to determine the genetic conditions of DMD mutation in fetus and mother, establish different data analysis methods and develop a novel noninvasive prenatal diagnosis for DMD fetus either inherited or caused by de novo exon deletions/duplications mutation.This method can detect > 178bp deletions/duplications within the captured DMD region no matter if the mutation exists or not on the maternal background, and is potentially applicable to non-invasive diagnosis of almost any genetic condition with small deletions/duplications mutation, rather than being limited to specific traits (such as the sex and aneuploidy of the fetus) like most previous methods.