Genetic Variation Analysis and Treatment Strategy of 20 Patients with Dystrophin Gene Mutations

Abstract

Background. Dystrophin (DMD) gene mutations canaffect muscular dystrophin isoform expression and result in progressive muscular dystrophy including Duchenne and Becker muscular dystrophies (DMD and BMD). To establish the correlation between phenotype and genotype and exemplify the current and future treatment for muscular dystrophy disorders, we investigated 20 patients suffering from a dystrophinopathy andsummarized clinical manifestation and gene mutations of them. Case presentation.The clinical manifestations, physical examination, laboratory work, and gene mutation results were collected in 20 patients with DMD or BMD diagnosed by clinical phenotype and genetic sequencing from July 2015 to December 2019. Multiplex ligation probe amplification (MLPA) and next-generation sequencing (NGS) were used to detect mutations in the DMD gene, and detected mutations were confirmed by Sanger sequencing. The clinical manifestation of patients was characterized by progressive symmetrical muscle degeneration, limb weakness, and pseudohypertrophy along with the elevated concentration of creatine kinase, alanine aminotransferase,and aspartate aminotransferase.We found 11 dystrophin gene deletions (55%) and 4 duplication mutations (20%) among the affected patients. However, we also found point mutations including 1 nonsense (20%), 3 frameshifts (60%), and 1 splice sites (20%) mutations in the rest 5 patients. Among the 15 cases of exon deletion or duplication mutations, 7 were inherited from the mother, 3 were de-novo, while the other 5 were not tested. Besides, all 5 point-mutation cases were inherited from the mother, among which 4 point mutations were identified for the first time and linked to the disease phenotype. Conclusions.We provided clinical portraits, genetic results, and the molecular effects of mutations in patients. Four novel point mutations were identified for the first time and associated with the development of DMD and BMD. Further, we expanded knowledge of the DMD variant spectrum and exemplified the emerging therapies in muscular dystrophy.