Qianwen Chen,1,2,* Wenjuan Zhang,2,3,* Lingfeng Zha2 

1Department 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; 2Department 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; 3Department of Geriatrics, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Lingfeng Zha, Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email zhalf@hust.edu.cn

Abstract: 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 DMD 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 DMD 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.

Keywords: DMD, MLPA, Sanger, exon skipping, personalized therapy