PDF(Pubmed)
Abstract：
Most pathogenic DMD variants are detectable and interpretable by standard genetic testing for dystrophinopthies. However, approximately 1∼3% of dystrophinopthies patients still do not have a detectable DMD variant after standard genetic testing, most likely due to structural chromosome rearrangements and/or deep intronic pseudoexon-activating variants. Here, we report on a boy with a suspected diagnosis of Becker muscular dystrophy (BMD) who remained without a detectable DMD variant after exonic DNA-based standard genetic testing. Dystrophin mRNA studies and genomic Sanger sequencing were performed in the boy, followed by in silico splicing analyses. We successfully detected a novel deep intronic disease-causing variant in the DMD gene (c.2380 + 3317A > T), which consequently resulting in a new dystrophin pseudoexon activation through the enhancement of a cryptic donor splice site. The patient was therefore genetically diagnosed with BMD. Our case report further emphasizes the significant role of disease-causing splicing variants within deep intronic regions in genetically undiagnosed dystrophinopathies.
摘要：
大多数致病性DMD变体可通过标准的肌营养不良基因检测来检测和解释。然而,大约1~3%的肌营养不良患者在标准基因检测后仍然没有可检测到的DMD变异，最有可能是由于结构染色体重排和/或深内含子假外显子激活变异。这里,我们报道了一名疑似诊断为Becker型肌营养不良症(BMD)的男孩,该男孩在基于外显子DNA的标准基因检测后仍未发现DMD变异.在男孩中进行了肌营养不良蛋白mRNA研究和基因组Sanger测序，其次是在硅剪接分析。我们成功地在DMD基因中检测到一种新的深层内含子致病变异（c.2380+3317A>T），因此，通过增强隐蔽的供体剪接位点，导致新的肌营养不良蛋白假外显子激活。因此，该患者被遗传诊断为BMD。我们的病例报告进一步强调了深层内含子区域内致病剪接变异在遗传未诊断的肌营养不良蛋白病中的重要作用。
