Genotype-phenotype correlation in Becker muscular dystrophy in Chinese patients

• Published in: Journal of human genetics 2018-10, Vol.63 (10), p.1041-1048
• Main Authors: Yuan, Ruiyi, Yi, Junfei, Xie, Zhiying, Zheng, Yimeng, Han, Miao, Hou, Yue, Wang, Zhaoxia, Yuan, Yun
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Asian Continental Ancestry Group - genetics; Becker's muscular dystrophy; Child; China; Dystrophin; Exon skipping; Female; Gene deletion; Genotype; Genotypes; Humans; Male; Muscle strength; Muscular dystrophy; Muscular Dystrophy, Duchenne - genetics; Mutation; Myopathy; Phenotype; Phenotypes; Quadriceps muscle
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/s10038-018-0480-5

Large deletions and duplications are the most frequent causative mutations in Becker muscular dystrophy (BMD), but genetic profile varied greatly among reports. We performed a comprehensive molecular investigation in 95 Chinese BMD patients. All patients were divided into three subtypes: normal muscle strength (type 1) in 18 cases, quadriceps myopathy (type 2) in 20 cases, and limb-girdle weakness (type 3) in 57 cases. Nineteen cases (20.0%) had small mutations and 76 cases (80.0%) had major rearrangements, including 67 cases (70.5%) of exonic deletions and 9 cases (9.5%) of exonic duplications. We identified 50 cases (65.8%) of in-frame mutations, and 26 cases (34.2%) of frame-shift mutations. The frequency of deletion in exons 13-19 was 30.6% in type 1 patients, 9.7% in type 2 patients, and 10.4% in type 3 patients. The frequency of deletion in exons 45-55 was 28.6% in type 1 patients, 40.8% in type 2, and 50.0% in type 3 patients. All major rearrangements of DMD gene in type 1 patients were also observed in type 3 patients. Our study suggested that frame-shift mutation was not rare in Chinese BMD patients. Although no difference was observed on the forms of DMD gene mutations among the three types of patients, the mutation in proximal region of DMD gene has higher frequency for patients without weakness. Effect of exon skipping for DMD depends on the size and location of the mutation. Additional studies are required to determine whether exon-skipping strategies in proximal region of DMD gene could yield more functional dystrophin.