Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
GrandOmics Biosciences, Beijing, China.
BMC Med Genomics. 2024 Sep 9;17(1):227. doi: 10.1186/s12920-024-01997-2.
Duchenne Muscular Dystrophy (DMD) is an X-linked disorder caused by mutations in the DMD gene, with large deletions being the most common type of mutation. Inversions involving the DMD gene are a less frequent cause of the disorder, largely because they often evade detection by standard diagnostic methods such as multiplex ligation probe amplification (MLPA) and whole exome sequencing (WES).
Our research identified two intrachromosomal inversions involving the dystrophin gene in two unrelated families through Long-read sequencing (LRS). These variants were subsequently confirmed via Sanger sequencing. The first case involved a pericentric inversion extending from DMD intron 47 to Xq27.3. The second case featured a paracentric inversion between DMD intron 42 and Xp21.1, inherited from the mother. In both cases, simple repeat sequences (SRS) were present at the breakpoints of these inversions.
Our findings demonstrate that LRS is an effective tool for detecting atypical mutations. The identification of SRS at the breakpoints in DMD patients enhances our understanding of the mechanisms underlying structural variations, thereby facilitating the exploration of potential treatments.
杜氏肌营养不良症（DMD）是一种 X 连锁疾病，由 DMD 基因突变引起，大片段缺失是最常见的突变类型。涉及 DMD 基因的倒位是该病不太常见的原因，主要是因为它们通常会逃避多重连接探针扩增（MLPA）和全外显子组测序（WES）等标准诊断方法的检测。
我们通过长读测序（LRS）在两个不相关的家庭中发现了两个涉及 dystrophin 基因的染色体内倒位。这些变体随后通过 Sanger 测序得到确认。第一个病例涉及从 DMD 内含子 47 延伸到 Xq27.3 的着丝粒内倒位。第二个病例是 DMD 内含子 42 和 Xp21.1 之间的旁侧倒位，由母亲遗传。在这两种情况下，倒位断点处都存在简单重复序列（SRS）。
我们的研究结果表明，LRS 是检测非典型突变的有效工具。在 DMD 患者的断点处鉴定出 SRS，增强了我们对结构变异机制的理解，从而促进了对潜在治疗方法的探索。
