Sheikh Omar, Yokota Toshifumi
Department of Medical Genetics, University of Alberta Faculty of Medicine and Dentistry, Edmonton, AB T6G 2H7, Canada.
The Friends of Garrett Cumming Research & Muscular Dystrophy Canada HM Toupin Neurological Science Research Chair, Edmonton, AB T6G 2H7, Canada.
J Pers Med. 2020 Sep 3;10(3):111. doi: 10.3390/jpm10030111.
Currently, Duchenne muscular dystrophy (DMD) and the related condition Becker muscular dystrophy (BMD) can be usually diagnosed using physical examination and genetic testing. While BMD features partially functional dystrophin protein due to in-frame mutations, DMD largely features no dystrophin production because of out-of-frame mutations. However, BMD can feature a range of phenotypes from mild to borderline DMD, indicating a complex genotype-phenotype relationship. Despite two mutational hot spots in dystrophin, mutations can arise across the gene. The use of multiplex ligation amplification (MLPA) can easily assess the copy number of all exons, while next-generation sequencing (NGS) can uncover novel or confirm hard-to-detect mutations. Exon-skipping therapy, which targets specific regions of the dystrophin gene based on a patient's mutation, is an especially prominent example of personalized medicine for DMD. To maximize the benefit of exon-skipping therapies, accurate genetic diagnosis and characterization including genotype-phenotype correlation studies are becoming increasingly important. In this article, we present the recent progress in the collection of mutational data and optimization of exon-skipping therapy for DMD/BMD.
目前，杜氏肌营养不良症（DMD）及相关的贝克肌营养不良症（BMD）通常可通过体格检查和基因检测来诊断。由于框内突变，BMD的特征是肌营养不良蛋白部分功能正常，而由于框外突变，DMD的主要特征是不产生肌营养不良蛋白。然而，BMD可表现出从轻度到临界DMD的一系列表型，这表明存在复杂的基因型-表型关系。尽管肌营养不良蛋白有两个突变热点，但整个基因都可能出现突变。多重连接依赖性探针扩增技术（MLPA）可轻松评估所有外显子的拷贝数，而新一代测序技术（NGS）则可发现新的或确认难以检测到的突变。外显子跳跃疗法是针对DMD的个性化医疗的一个突出例子，它根据患者的突变靶向肌营养不良蛋白基因的特定区域。为了使外显子跳跃疗法的益处最大化，包括基因型-表型相关性研究在内的准确基因诊断和特征分析变得越来越重要。在本文中，我们介绍了DMD/BMD突变数据收集和外显子跳跃疗法优化方面的最新进展。
