关键词: Duchenne肌营养不良, 基因治疗, 外显子, 重复, 缺失, 点变异

Abstract:

Objective To investigate the characteristics of clinical phenotype and genotype in children with Duchenne muscular dystrophy (DMD). Methods The clinical data of 171 children diagnosed with DMD by clinical and genetic tests from January 2014 to June 2020 were collected, and the clinical manifestations and genetic variation results were analyzed. Results The median age of 171 DMD children (165 boys and 6 girls) was 4.1 (1.7-7.0) years. Among them, 21 children were younger than 1 year old, 41 children were 1-3 years old, 65 children were 3-7 years old, and 44 children were 7-13 years old. The main clinical manifestations of 171 children were motor development retardation, increased muscle enzymes and limb weakness. The first visit to the neurology department of the infants and young children was mainly due to the elevated muscle enzymes (including creatine kinase, creatine kinase isoenzyme and lactate dehydrogenase). Compared with the young children group, the infant group had a higher proportion of first visits to the neurology department due to increased muscle enzymes, and a lower proportion of visits due to motor development retardation, with statistically significant differences (P<0.05). Hormone therapy improved the condition of most children. DMD genes were mostly largely deletions (111 cases, 64.9%) by high-throughput sequencing techniques. There were 26 cases (15.2%) with large duplication variations and 34 cases (19.9%) with point variations. The variation could occur anywhere in the gene, but there were two deletion hotspots, which were located in the central exon 45-52 region (76 cases, accounting for 68.5% of the large deletion variations) and in the exon 2-28 region of 5' end (21 cases, accounting for 18.9% of the large deletion variations). Conclusions Increased muscle enzymes and limb weakness are the main clinical manifestations of DMD children, and genetic testing should be conducted in time if abnormalities are found. Understanding the clinical manifestations and genotype characteristics of DMD is very important for its prevention, management and treatment.

Key words: Duchenne muscular dystrophy, gene therapy, exon, duplication, deletion, point variation