PDF(Pubmed)
Abstract：
UNASSIGNED: Duchenne muscular dystrophy (DMD) (NM_004006.3) is one of the most notable neuromuscular disorders of early years. The majority of DMD cases are caused by deletions or duplications in dystrophin, while point mutations are less prevalent in dystrophin abnormalities. It is a common knowledge that the severity of the disease depends on the effect of the mutation on the translational reading frame of the dystrophin mRNA.
UNASSIGNED: We studied an 8-year-old boy with relevant clinical presentations for DMD. Deletion/duplication screening was performed by using multiplex ligation-dependent probe amplification, and whole-exome sequencing was conducted in order to identify potential variants. A novel de novo splice site variant was identified in the DMD gene (DMD: c.8548-2A>G). To explore the effect of a novel variant in DMD, various in silico analyses were carried out to investigate the pathogenicity of the causative variant. To study the structure of a DMD protein and information on how the genetic variant impacts splicing site in models of wild-type and mutated DMD, we carried out different computational studies. Sanger sequencing was performed for the purpose of variant confirmation and familial segregation analysis.
UNASSIGNED: This novel de novo variant was predicted to have an effect on splicing, which leads to DMD due to its significant impacts on dystrophin functionality. The novel mutation would be expected to disrupt the protein structure.
UNASSIGNED: We studied an 8-year-old boy with relevant clinical presentations for DMD. Deletion/duplication screening was performed by using multiplex ligation-dependent probe amplification, and whole-exome sequencing was conducted in order to identify potential variants. A novel de novo splice site variant was identified in the DMD gene (DMD: c.8548-2A>G). To explore the effect of a novel variant in DMD, various in silico analyses were carried out to investigate the pathogenicity of the causative variant. To study the structure of a DMD protein and information on how the genetic variant impacts splicing site in models of wild-type and mutated DMD, we carried out different computational studies. Sanger sequencing was performed for the purpose of variant confirmation and familial segregation analysis.
UNASSIGNED: This novel de novo variant was predicted to have an effect on splicing, which leads to DMD due to its significant impacts on dystrophin functionality. The novel mutation would be expected to disrupt the protein structure.
摘要：
■杜氏肌营养不良症（DMD）（NM_004006.3）是早年最著名的神经肌肉疾病之一。大多数DMD病例是由肌营养不良蛋白的缺失或重复引起的，而点突变在肌营养不良蛋白异常中的发生率较低。众所周知，疾病的严重程度取决于突变对肌营养不良蛋白mRNA翻译阅读框的影响。
■我们研究了一个8岁男孩的DMD临床表现。通过使用多重连接依赖性探针扩增进行缺失/重复筛选，进行全外显子组测序以鉴定潜在的变异体。在DMD基因中鉴定了新的从头剪接位点变体(DMD:c.8548-2A>G)。为了探索DMD中新型变体的作用，进行了各种计算机模拟分析，以研究致病变异的致病性。为了研究DMD蛋白的结构以及在野生型和突变DMD模型中遗传变异如何影响剪接位点的信息，我们进行了不同的计算研究。为了变体确认和家族分离分析的目的,进行Sanger测序。
■预测这种新的从头变体对剪接有影响，由于其对肌营养不良蛋白功能的显著影响，导致DMD。预期新的突变会破坏蛋白质结构。
■我们研究了一个8岁男孩的DMD临床表现。通过使用多重连接依赖性探针扩增进行缺失/重复筛选，进行全外显子组测序以鉴定潜在的变异体。在DMD基因中鉴定了新的从头剪接位点变体(DMD:c.8548-2A>G)。为了探索DMD中新型变体的作用，进行了各种计算机模拟分析，以研究致病变异的致病性。为了研究DMD蛋白的结构以及在野生型和突变DMD模型中遗传变异如何影响剪接位点的信息，我们进行了不同的计算研究。为了变体确认和家族分离分析的目的,进行Sanger测序。
■预测这种新的从头变体对剪接有影响，由于其对肌营养不良蛋白功能的显著影响，导致DMD。预期新的突变会破坏蛋白质结构。
