Table_2_A Comprehensive Analysis of 2013 Dystrophinopathies in China: A Report From National Rare Disease Center.DOCX

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive neuromuscular disorders caused by mutations in DMD. A high-quality database of DMD/BMD is essential not only for clinical practice but also for fundamental research. Here, we aimed to build the largest Chinese national dystrophinopathy database using the National Rare Diseases Registry System of China. Peking Union Medical College Hospital (PUMCH) was the National Rare Diseases Center of China. This research involved 2013 patients with dystrophinopathies, whose diagnoses were confirmed; they were registered and followed up at PUMCH from March 2011 to December 2018. Family history, clinical signs, and treatment data were reported for patients with DMD and BMD at different rates. All six serum biochemical indexes could accurately distinguish between DMD and BMD patients. Copy number variations were the most frequent mutation type (79.2% in DMD and 84.3% in BMD), of which large deletions accounted for 88.4 and 88.6%, large duplications accounted for 11.6 and 11.4% in DMD and BMD, respectively. An exon deletion hotspot, located in exons 45–54, was observed in DMD, and intron 44 was the most frequent deletion starting point (26.5%). Duplication and single nucleotide variations appeared to be uniformly distributed among all exons. Eleven patients were identified to have ultrarare mutation types. Eleven other patients suffered from two separate mutations simultaneously, some of which may have taken place via dependent mechanisms. Thus, we have established the largest hospital-based Chinese dystrophinopathy database via the National Rare Diseases Registry System. This study provides valuable information for further diagnostic and therapeutic studies of dystrophinopathy.

杜氏肌营养不良症（Duchenne muscular dystrophy, DMD）与贝克型肌营养不良症（Becker muscular dystrophy, BMD）均为X连锁隐性遗传性神经肌肉疾病，致病根源为DMD基因突变。高质量的DMD/BMD数据库不仅是临床诊疗实践的必要支撑，亦是开展相关基础研究的重要基础。本研究依托中国国家罕见病注册登记系统，旨在构建国内规模最大的肌营养不良蛋白病（dystrophinopathy）数据库。北京协和医院（Peking Union Medical College Hospital, PUMCH）作为中国国家罕见病诊疗中心，纳入了2013例经确诊的肌营养不良蛋白病患者；这些患者于2011年3月至2018年12月期间在北京协和医院完成注册并接受随访。针对DMD与BMD患者，本研究按不同收集比例记录了其家族史、临床体征与治疗相关数据。六项血清生化指标均可精准区分DMD与BMD患者。拷贝数变异（Copy Number Variation）是最常见的突变类型：在DMD患者中占比79.2%，在BMD患者中占比84.3%；其中大片段缺失在DMD患者中占该类变异的88.4%、大片段重复占11.6%，在BMD患者中大片段缺失占88.6%、大片段重复占11.4%。在DMD患者中观察到外显子45-54区域存在外显子缺失热点，内含子44是最常见的缺失起始位点（占比26.5%）。大片段重复与单核苷酸变异（Single Nucleotide Variation）则在所有外显子区域呈均匀分布。另有11例患者被检出极为罕见的突变类型。另有11例患者同时携带两种独立突变，其中部分突变可能通过依赖型机制发生。综上，本研究依托中国国家罕见病注册登记系统，构建了目前国内规模最大的以医院为基础的肌营养不良蛋白病数据库。本研究可为肌营养不良蛋白病后续的诊断与治疗研究提供极具价值的参考依据。