45例Duchenne型肌营养不良症患者DMD基因微小突变分析

Tiny mutations of Duchenne muscular dystrophy gene in 45 patients with Duchenne muscular dystrophy

目的探讨Duchenne型肌营养不良症（DMD）基因点突变、微小缺失或插入突变的特征。方法选择自2011年1月至2016年11月中山大学附属第一医院神经肌肉病专科门诊收治的DMD患者，采用二代测序技术，对经多重连接探针扩增技术（MLPA）检测证实为非缺失／非重复突变的、临床诊断为DMD的45例患者，进行DMD基因测序，并对其微小突变的特点进行分析和总结。结果在45例非缺失／非重复突变的DMD患者中．共检出66个突变，其中错义突变24个，无义突变20个，剪接位点突变12个，移码突变9个，同义突变1个；携带1个突变患者29例，携带2个突变8例，携带3个突变4例，携带4个突变3例，携带5个突变1例；以外显子48发生错义突变最常见，其次为外显子37和外显子59；无义突变、移码突变、剪接位点突变、同义突变未见明显的集中分布趋势。结论针对微小突变的治疗药物研发应先重点考虑外显子48、37、59这3个区域，无义突变更适合使用无义突变通读治疗。

Objective To investigate the characteristics of point mutation, deletion or insertion mutations in Duchenne muscular dystrophy （DMD） gene. Methods Clinically confirmed 45 DMD patients without deletion/duplication mutation confirmed by MLPA in our hospital from January 2011 to November 2016 were chosen. Two generation sequencing technology was employed to detect DMD gene sequences. The features of tiny mutations were analyzed and summarized. Results In 45 patients without deletion/repeat mutation DMD, there were 66 mutations, including 24 missense mutations, 20 nonsense mutations, 12 splice site mutations, 9 frameshift mutations and one synonymous mutation. There were 29 patients carrying one mutation, 8 patents carrying 2 mutations, 4 patients carrying 3 mutations, 4 patients carrying 3 mutations, and one patient carrying 5 mutations. The exon 48 missense mutations were the most common, followed by exon 37 and exon 59; nonsense mutations, frameshift mutations, splice site mutations, and synonymous mutations had no obvious concentration distribution trend. Conclusion The exons 48, 37 and 59 should be mainly considered during the drug research and development of tiny mutations, and readingthrough treatment of nonsense mutations is suitable for nonsense mutations.