Abstract：
Structural variants (SVs) are infrequently observed in Duchenne muscular dystrophy (DMD), a condition mainly marked by deletions and point mutations in the DMD gene. SVs in DMD remain difficult to reliably detect due to the limited SV-detection capacity of conventionally used short-read sequencing technology. Herein, we present a family, a boy and his mother, with clinical signs of muscular dystrophy, elevated creatinine kinase levels, and intellectual disability. A muscle biopsy from the boy showed dystrophin deficiency. Routine molecular techniques failed to detect abnormalities in the DMD gene, however, dystrophin mRNA transcripts analysis revealed an absence of exons 59 to 79. Subsequent long-read whole-genome sequencing identified a rare complex structural variant, a 77 kb novel intragenic inversion, and a balanced translocation t(X;1)(p21.2;p13.3) rearrangement within the DMD gene, expanding the genetic spectrum of dystrophinopathy. Our findings suggested that SVs should be considered in cases where conventional molecular techniques fail to identify pathogenic variants.
摘要：
在杜兴氏肌营养不良症（DMD）中很少观察到结构变异（SV），一种主要以DMD基因缺失和点突变为特征的病症。由于常规使用的短读测序技术的有限的SV检测能力,DMD中的SV仍然难以可靠地检测。在这里，我们呈现一个家庭，一个男孩和他的母亲，有肌营养不良的临床症状，肌酐激酶水平升高，智力残疾。男孩的肌肉活检显示肌营养不良蛋白缺乏。常规分子技术未能检测到DMD基因的异常，然而,肌营养不良蛋白mRNA转录本分析显示缺乏外显子59至79。随后的长读全基因组测序发现了一个罕见的复杂结构变异，一个77kb的新颖基因内倒置，和DMD基因内的平衡易位t(X;1)(p21.2;p13.3)重排，扩大肌萎缩蛋白病的遗传范围。我们的发现表明，在常规分子技术无法识别致病变体的情况下，应考虑SV。
