Background Duchenne Muscular Dystrophy (DMD) is a progressive, fatal neuromuscular disorder caused by mutations in the DMD gene. Emerging antisense oligomer based exon skipping therapy provides hope for the restoration of the reading frame. Objectives Population-based DMD mutation database may enable exon skipping to be used for the benefit of patients. Hence, we planned this study to identify DMD gene variants in North Indian DMD cases. Methods A total of 100 DMD cases were recruited and Multiplex ligation-dependent probe amplification (MLPA) analysis was performed to obtain the deletion and duplication profile. Results Copy number variations (deletion/duplication) were found in 80.85% of unrelated DMD cases. Sixty-eight percent of cases were found to have variations in the distal hotspot region (Exon 45-55) of the DMD gene. Exon 44/45 variations were found to be the most prominent among single exon variations, whereas exon 49/50 was found to be the most frequently mutated locations in single/multiple exon variations. As per Leiden databases, 86.84% cases harboured out-of-frame mutations. Domain wise investigation revealed that 68% of mutations were localized in the region of spectrin repeats. Dp140 isoform was predicted to be absent in 62/76 (81.57%) cases. A total of 45/80 (56.25%) and 23/80 (28.70%) DMD subjects were predicted to be amenable to exon 51 and exon 45 skipping trials, respectively. Conclusion A major proportion of DMD subjects (80%) could be diagnosed by the MLPA technique. The data generated from our study may be beneficial for strengthening of mutation database in the North Indian population.

中文翻译：

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重新利用 DMD 基因的致病变异及其同种型用于 DMD 外显子跳跃干预

背景 Duchenne Muscular Dystrophy (DMD) 是一种由 DMD 基因突变引起的进行性、致命的神经肌肉疾病。新兴的基于反义寡聚体的外显子跳跃疗法为恢复阅读框提供了希望。目标 基于人群的 DMD 突变数据库可以使外显子跳跃用于患者的利益。因此，我们计划进行这项研究以识别北印度 DMD 病例中的 DMD 基因变异。方法共招募100例DMD病例，进行多重连接依赖探针扩增（MLPA）分析，获得缺失和重复谱。结果 在 80.85% 的无关 DMD 病例中发现了拷贝数变异（删除/重复）。发现 68% 的病例在 DMD 基因的远端热点区域（外显子 45-55）中存在变异。外显子 44/45 变异被发现是单外显子变异中最突出的，而外显子 49/50 被发现是单/多外显子变异中最常见的突变位置。根据 Leiden 数据库，86.84% 的病例存在框外突变。领域调查显示，68% 的突变位于血影蛋白重复区域。预计 62/76 (81.57%) 病例中不存在 Dp140 异构体。预计共有 45/80 (56.25%) 和 23/80 (28.70%) 的 DMD 受试者分别适合外显子 51 和外显子 45 跳跃试验。结论 大部分 DMD 受试者（80%）可以通过 MLPA 技术进行诊断。我们研究产生的数据可能有利于加强北印度人群的突变数据库。