摘要
目的分析Duchenne型进行性肌营养不良(DMD)患儿的临床和基因突变特点,总结并分析97例DMD病例的基因突变热点。方法收集2014年1月至2018年1月上海交通大学医学院附属上海儿童医学中心通过基因检查随访确诊为DMD的患儿97例,对其临床表现,生化检查和基因突变结果进行分析。结果 97例中男96例,主要以喂养困难、肌酶增高和肢体无力为主要临床表现。肌酸激酶(CK)、乳酸脱氢酶(LDH)和天冬氨酸转移酶(AST)等肌酶均明显升高。通过组合的高通量检测技术检查DMD基因多为大缺失,共62例(63.92%),大重复突变11例(11.34%),24例(24.74%)发生点突变。所有的突变可发生在基因的任何位置,但是有两个缺失的热点区域:位于基因的中央区外显子45～55区共45例,占大缺失突变的72.58%;位于5’端外显子2～19区12例,占大缺失突变的19.35%。结论喂养困难、肌酶增高和肢体无力为DMD患儿的主要临床表现。肌酶明显增高者DMD基因应及时检测。
Objective(DMD),summarize the gene mutation hotspots in 97 cases and to explore the correlation between clinical manifestations and genotype. Methods Totally 97 patients with DMD diagnosed by genetic examination from January 2014 to 2018 were collected and analyzed. The clinical manifestations,serum analyses and gene mutation results were analyzed. Results The main clinical manifestations of 97 patients(96 boys)were feeding difficulties,increased muscle enzyme and limb weakness.Creatine kinase(CK),lactate dehydrogenase(LDH)and aspartate aminotransferase(AST)muscle enzymes were significantly increased. By combining deep-sequencing technologies,the large deletions of DMD gene mutation was in 62 cases(63.92%);there were 11 cases(11.34%)of large duplication mutation,and 24 cases(24.74%)of point mutation. All of the mutations could occur in any position in the DMD gene,but there were two hot spots;45 cases were located in the central region gene exon 45～55(72.58%);12 cases of deletion mutation were located in 5'exon end exon 2～19 area(19.35%). Conclusion The main clinical manifestations of the DMD children are feeding difficulty,increased muscle enzyme and limb weakness.The patients with significantly increased muscle enzyme should receive a timely defection of DMD gene.
引文
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