Comparison of the phenotypes of patients harboring in-frame deletions starting at exon 45 in the Duchenne muscular dystrophy gene indicates potential for the development of exon skipping therapy
Comparison of the phenotypes of patients harboring in-frame deletions starting at exon 45 in the Duchenne muscular dystrophy gene indicates potential for the development of exon skipping therapy
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DOI：
10.1038/jhg.2016.152
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发表时间：
2017-04-01
影响因子：
3.5
通讯作者：
Yokota, Toshifumi
中科院分区：
文献类型：
--
作者：
Nakamura, Akinori;Shiba, Naoko;Yokota, Toshifumi
外显子跳跃疗法最近因其通过校正开放阅读框架将致死性杜氏肌营养不良症（DMD）的表型转化为更良性的形式贝克尔肌营养不良症（BMD）的能力而受到关注。这种疗法主要集中在DMD基因中的热点（外显子45-55）突变。外显子45-55的整个延伸的外显子跳跃是适用于46.9%的DMD患者的方法。然而，由此产生的表型尚未完全理解。在这里，我们研究了24例BMD患者的临床资料，从外显子45开始缺失。Delta 45-55组的年龄范围为2 - 87岁;未观察到死亡，1例患者在79岁时可以走动。45 -48岁组（18-88岁）中患者坐轮椅的年龄约为50岁。在两个删除组中，心肌病都得到了药物的良好控制。相比之下，0.45 -47和Delta 45-49组表现出比其他突变更严重的表型：Delta 45-49组患者坐轮椅的年龄约为30-40岁。我们的研究表明，临床严重程度不同之间的每个热点删除。
Exon skipping therapy has recently received attention for its ability to convert the phenotype of lethal Duchenne muscular dystrophy (DMD) to a more benign form, Becker muscular dystrophy (BMD), by correcting the open reading frame. This therapy has mainly focused on a hot-spot (exons 45-55) mutation in the DMD gene. Exon skipping of an entire stretch of exons 45-55 is an approach applicable to 46.9% of DMD patients. However, the resulting phenotype is not yet fully understood. Here we examined the clinical profiles of 24 patients with BMD resulting from deletions starting at exon 45. The Delta 45-55 group ranged in age from 2 to 87 years; no mortality was observed, and one patient was ambulatory at 79 years of age. The age at which patients became wheelchair-bound in the.45-48 group (18-88 years old) was approximately 50 years. Cardiomyopathy was well controlled by pharmaceuticals in both deletion groups. In contrast, the.45-47 and Delta 45-49 groups exhibited more severe phenotypes than those with other mutations: the age at which patients in the Delta 45-49 group became wheelchair-bound was around 30-40 years. Our study shows that clinical severity differs between each hot-spot deletion.