Clinical And Genetic Analysis Of Affected Male And Symptomatic Female Carriers With Duchenne/Becker Muscular Dystrophy In Guangxi

Objective This study aims to analyze the clinical characterization in the patients with Duchenne/Becker muscular dystrophy. We also analyze the mutation of dystrophin gene in patients and genotype-phenotype correlation.Methods The data of retrospective analysis is from the children with clinical diagnosis of DMD/BMD.Results(1). Sixty-six patients were included in this study, sixty-two patients male and four cases of symptomatic female carriers. The most common reason of attending hospital is the elevated serum CK activity or ALT and AST (45.45%, 30/66). From the data of male patients, serum CK, AST, ALT were all remarkably higher than the reference value and gradually reduced with clinical progression and age increasing. we found linear correlations between CK and AST (r=0.691, p<0.01, CK and ALT (r=0.416, p<0.01).(2). Analysis of echocardiography was performed in 40 cases, one’s echocardiography showed enlargement of the left ventricle with severely reduced left ventricular function and mitral regurgitation; 38 cases underwent a calf muscle biopsy, the pathology showed varying degree atrophy, degeneration and necrosis in muscle fiber, skeletal muscle fuzzy, interstitial fibers and adipose tissue filling the atrophy of muscle fiber, among these with only two cases accompanied with inflammatory cell infiltration.(3). All cases were analyzed the mutation in the dystrophin gene with MLPA. Among 62 boys,46cases (74.19%) obtained a positive result.42 cases (67.7%) had deletions of the dystrophin gene exons and the deletion hotspot region towards the central part of the gene (exons 45-55), followed by exon 2-19(11.9%), duplications were detected in 4 cases (6.45%) and the mutation site towards the 3’end,16 cases did not shown any mutation. Among 46 cases, 42 cases were frame shift mutation, while 4 cases were in-frame mutation,43 cases were DMD phenotype, only one case of BMD phenotype, but the two reminders was unclear, this reading frame hypothesis holds for 98.3% of cases. In 4 symptomatic female carriers, three cases had the duplications of the dystrophin gene, while the remaining one did not show any mutation.Conclusions(1).The CK, AST, ALT activity were significantly increased, serum enzymes showed a linear correlation between CK and AST or CK and ALT in male patients. However, a few heterozygous female carriers of DMD mutations are symptomatic and serum CK levels are elevated in all of symptomatic female carriers. (2).Mutations of dystrophin gene can be in various forms, the deletion mutation of dystrophin gene is the most common changes and also it has deletion mutation hot spot and duplication breakpoints were clustered at the 3’ end of the dystrophin gene. Clinical form of the disease has no relationship with the size of mutation, and it depends on maintaining or disrupting the reading frame (in frame mutation leads to BMD, out of frame mutation leads to DMD).(3). MLPA technique is a reliable, quick, convenient method for detection deletions and duplications in male patients and symptomatic female carriers, a sensitivity of detecting DNA rearrangement by MLPA of 74.19%.