Wang Dan-Ni, Wang Zhi-Qiang, Yan Lei, He Jin, Lin Min-Ting, Chen Wan-Jin, Wang Ning
Department of Neurology and Institute of Neurology, First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Department of Neurology and Institute of Neurology, First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Molecular Neurology, Fuzhou, China.
Neuromuscul Disord. 2017 Aug;27(8):715-722. doi: 10.1016/j.nmd.2017.02.010. Epub 2017 Feb 21.
The development of clinical trials for Duchenne muscular dystrophy (DMD) in China faces many challenges due to limited information about epidemiological data, natural history and clinical management. To provide these detailed data, we developed a comprehensive database based on registered DMD patients from South China and analysed their clinical and mutational characteristics. The database included DMD registrants confirmed by clinical presentation, family history, genetic detection, prognostic outcome, and/or muscle biopsy. Clinical data were collected by a registry form. Mutations of dystrophin were detected by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. Currently, 132 DMD patients from 128 families in South China have been registered, and 91.7% of them were below 10 years old. In mutational detection, large deletions were the most frequent type (57.8%), followed by small deletion/insertion mutations (14.1%), nonsense mutations (13.3%), large duplications (10.9%), and splice site mutations (3.1%). Clinical analysis revealed that most patients reported initial symptoms between 1 and 3 years of age, but the diagnostic age was more frequently between 6 and 8 years. 81.4% of patients were ambulatory. Baseline cardiac assessments at diagnosis were conducted in 39.4% and 29.5% of patients by echocardiograms and electrocardiograms, respectively. Only 22.7% of registrants performed baseline respiratory assessments. A small numbers of patients (20.5%) were treated with glucocorticoids. 13.3% of patients were eligible for stop codon read-through therapy, and 48.4% of patients would potentially benefit from exon skipping. The top five exon skips applicable to the largest group of registrants were skipping of exons 51 (14.8% of total mutations), 53 (12.5%), 45 (7.0%), 55 (4.7%), and 44 (3.9%). In conclusion, our database provided information on the natural history, diagnosis and management status of DMD in South China, as well as potential molecular therapies suitable for these patients. This comprehensive database will promote future experimental therapies in China.
由于关于流行病学数据、自然病史和临床管理的信息有限，中国杜氏肌营养不良症（DMD）的临床试验发展面临诸多挑战。为了提供这些详细数据，我们基于来自中国南方登记的DMD患者开发了一个综合数据库，并分析了他们的临床和突变特征。该数据库包括通过临床表现、家族史、基因检测、预后结果和/或肌肉活检确诊的DMD登记者。临床数据通过登记表收集。通过多重连接依赖探针扩增（MLPA）和桑格测序检测肌营养不良蛋白的突变。目前，中国南方128个家庭的132名DMD患者已登记在册，其中91.7%年龄在10岁以下。在突变检测中，大片段缺失是最常见的类型（57.8%），其次是小缺失/插入突变（14.1%）、无义突变（13.3%）、大片段重复（10.9%）和剪接位点突变（3.1%）。临床分析显示，大多数患者报告的初始症状出现在1至3岁之间，但诊断年龄更常见于6至8岁。81.4%的患者能够行走。诊断时分别有39.4%和29.5%的患者通过超声心动图和心电图进行了基线心脏评估。只有22.7%的登记者进行了基线呼吸评估。少数患者（20.5%）接受了糖皮质激素治疗。13.3%的患者符合终止密码子通读疗法的条件，48.4%的患者可能从外显子跳跃中获益。适用于最大登记人群组的前五个外显子跳跃是外显子51的跳跃（占总突变的14.8%）、外显子53（12.5%）、外显子45（7.0%）、外显子55（4.7%）和外显子44（3.9%）。总之，我们的数据库提供了中国南方DMD的自然病史、诊断和管理状况以及适合这些患者的潜在分子疗法的信息。这个综合数据库将推动中国未来的实验性治疗。
