脊肌萎缩症是全球最常见的致死性常染色体隐性遗传性疾病之一，81%~95%的患者是由位于5q13的生存运动神经元基因SMN1的7号外显子纯合缺失导致，与其序列高度相似的SMN2是影响病情严重程度的修饰基因。脊肌萎缩症目前无有效的治疗方法，产前诊断是预防患儿出生最有效的措施。本研究针对先证者为SMN1基因7号外显子纯合缺失型脊肌萎缩症的产前诊断家系，以孕妇血浆游离DNA作为材料，选择高度杂合SNP位点进行多重cSMART检测，研究精确、快捷、低廉的胎源DNA含量定量方法；对基因和对照保守区域实行目标捕获和高通量测序，利用SMN1、SMN2差异性碱基进行序列比对，结合胎源DNA含量和母亲基因型，开发数据分析流程，实现对胎儿SMN1、SMN2基因拷贝数的准确计数，克服传统侵入性产前诊断和循环细胞法产前检测的缺陷，建立基于新一代测序的脊肌萎缩症无创产前检测方法。

Spinal muscular atrophy is one of the most common mortality-causing autosomal recessive diseases in the world. 81%~95% of SMA patients are caused by the homozygous deletion of exon 7 of the survival motor neuron 1 (SMN1) gene. For now, there is no effective therapy, and prenatal diagnosis is the most effective prevention. In this study, we plan to collect prenatal samples by families in which the probands have SMN1 exon 7 homozygous deletions, take maternal cell-free DNA as materials, test SNPs with high heterozygosity with self-developed multiple cSMART technology, invent methods to precisely, quickly and cost-effectively quantify the fetal DNA concentration. We will perform target capture and next-generation sequencing in the SMN and control gene regions, align the reads by the different base between SMN1 and SMN2, combine the cffDNA concentration and maternal genotype, develop data-analysis protocols to achieve the accurate copy numbers of SMN1 and SMN2, and establish the NGS-based SMA non-invasive prenatal testing method without the defects of traditional invasive prenatal diagnosis and the tests using circulation fetal cells.