Chen Qianwen, Zhang Wenjuan, Zha Lingfeng
Department of Pediatric Cardiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People's Republic of China.
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
Pharmgenomics Pers Med. 2025 Jun 17;18:153-162. doi: 10.2147/PGPM.S514145. eCollection 2025.
Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disease that is characterized by progressive proximal muscle weakness and pseudohypertrophy. Currently, genetic diagnosis of DMD relies largely on multiplex ligation-dependent probe analysis (MLPA) and Sanger sequencing to identify pathogenic mutations. This study aimed to confirm the genetic etiology of a boy presenting with clinical manifestations that are highly indicative of DMD. A 14-year-old boy with heart failure and extreme muscle weakness along with his family members was recruited for this study. DNA from each participant was isolated from peripheral blood samples. We used MLPA to detect the deletion or duplication mutations of the gene and Sanger sequencing to verify the missing region of the exon in the proband. Furthermore, the functional role of the mutation was assessed using bioinformatics. We found that the proband carried a small deletion in the gene (c.6808_6811delTTAA). The deletion of those four nucleotides resulted in a frameshift mutation and a premature nonsense codon, which resulted in a truncated dystrophin that lost its most critical function and underwent post-transcriptional degradation. Our study demonstrated that MLPA, in combination with Sanger sequencing, is a reliable and practical approach for the genetic diagnosis of DMD, which is a significant step towards developing personalized therapy.
杜氏肌营养不良症（DMD）是一种X连锁隐性神经肌肉疾病，其特征为进行性近端肌无力和假性肥大。目前，DMD的基因诊断主要依赖多重连接依赖探针分析（MLPA）和桑格测序来识别致病突变。本研究旨在确认一名临床表现高度提示DMD的男孩的遗传病因。一名患有心力衰竭和极度肌无力的14岁男孩及其家庭成员被招募参与本研究。从每个参与者的外周血样本中分离DNA。我们使用MLPA检测该基因的缺失或重复突变，并使用桑格测序验证先证者中外显子的缺失区域。此外，使用生物信息学评估该突变的功能作用。我们发现先证者在该基因中存在一个小的缺失（c.6808_6811delTTAA）。这四个核苷酸的缺失导致移码突变和过早的无义密码子，从而产生截短的抗肌萎缩蛋白，该蛋白失去了其最关键的功能并经历转录后降解。我们的研究表明，MLPA与桑格测序相结合是DMD基因诊断的一种可靠且实用的方法，这是朝着开发个性化治疗迈出的重要一步。
