Identifying inversions with breakpoints in the Dystrophin gene through long-read sequencing: report of two cases

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY
Liqing Chen, Xiaoping Luo, Hongling Wang, Yu Tian, Yan Liu
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引用次数: 0

Abstract

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.
通过长线程测序鉴定肌营养不良蛋白基因中的断点倒位:两个病例的报告
杜氏肌肉萎缩症(DMD)是一种由 DMD 基因突变引起的 X 连锁疾病,大缺失是最常见的突变类型。涉及 DMD 基因的倒位是一种不太常见的疾病病因,这主要是因为它们通常无法被标准诊断方法(如多重连接探针扩增(MLPA)和全外显子组测序(WES))检测到。 我们的研究通过长读测序(LRS)在两个没有血缘关系的家庭中发现了两个涉及肌营养不良症基因的染色体内倒位。这些变异随后通过桑格测序得到证实。第一个病例涉及从 DMD 内含子 47 扩展到 Xq27.3 的同中心倒位。第二个病例的特点是在 DMD 内含子 42 和 Xp21.1 之间的旁中心倒位,由母亲遗传。在这两个病例中,简单重复序列(SRS)都出现在这些倒位的断点处。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 患者的断点处发现 SRS 有助于加深我们对结构变异机制的了解,从而有助于探索潜在的治疗方法。
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来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
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