目的探讨糖皮质激素治疗假肥大型肌营养不良的最佳时期,以及分析失去行走能力(loss of ambulation,LoA)和抗肌萎缩蛋白基因(dystrophin,DMD)突变类型之间的关系。方法回顾性分析2008年5月至2021年5月在湖南省儿童医院确诊的假肥大型肌...目的探讨糖皮质激素治疗假肥大型肌营养不良的最佳时期,以及分析失去行走能力(loss of ambulation,LoA)和抗肌萎缩蛋白基因(dystrophin,DMD)突变类型之间的关系。方法回顾性分析2008年5月至2021年5月在湖南省儿童医院确诊的假肥大型肌营养不良患者的临床及遗传学数据。运用Cox比例风险模型(Cox proportional hazards model)分析服用激素起始年龄、康复训练时间以及基因型对患者独立行走时间的影响。结果共纳入437例患者,年龄集中在3~6岁,主要就诊原因为肌无力。遗传学检测依次发现的类型为DMD基因缺失(289例,61.1%)、点突变(148例,31.3%)、基因重复(36例,7.6%),其中点突变以无义突变(72例,64.3%)最常见。在3~5岁服用激素的患者[P<0.1,HR=0.47,中位数年龄13(13-NA)]丧失行走年龄显著比未用激素的患者晚。外显子43(Exon43)缺失突变[P<0.1,HR=3.04,中位数年龄10(10-NA)]的患者失去行走能力年龄显著早于“其他基因型”缺失。康复训练时间大于1年的患者丧失行走能力时间显著晚于未进行康复训练患者。结论患者在3~5岁服用激素效果最佳;进行1年以上的康复训练,有助于维持患者的独立行走时间;Exon43缺失突变的DMD患者具有较早的LoA,这将对临床试验设计方面带来益处。展开更多
Objective: Duchenne and Becker muscular dystrophy (DMD/BMD) is an X-linked lethal recessive disease caused by mutations in the dystrophy gene. There is no efficient treatment for this serious and disabling disease. We...Objective: Duchenne and Becker muscular dystrophy (DMD/BMD) is an X-linked lethal recessive disease caused by mutations in the dystrophy gene. There is no efficient treatment for this serious and disabling disease. We established a combination method to detect carriers and perform prenatal diagnosis. Methods: In our study, from 1994 to 2005, using a different combination of 5 methods, including SRY gene amplification, multiplex PCR, multiplex Fluorescence PCR capillary electrophoresis, multiplex ligation-dependent probe amplification (MLPA) and linkage analysis of short tandem repeats (STR), 36 prenatal diagnosis were performed for pregnancies at risk of having a DMD/BMD baby through amniocentesis. Results: Fourteen out of 21 male fetuses were found to be affected and respective pregnancies were terminated. A combined diagnostic rate of 83% was achieved for 30 cases with deletions, duplications, and non-deletion mutations after tested by more than one method. Conclusion: Using a combined method, we can diagnoses patients and carriers in DMD families, and perform prenatal diagnosis for the risk fetus. MLPA provides a simple, rapid and accurate method for deletions and duplications of all the 79 DMD exons. MLPA method for DMD diagnosis is the first report in our country.展开更多
文摘Objective: Duchenne and Becker muscular dystrophy (DMD/BMD) is an X-linked lethal recessive disease caused by mutations in the dystrophy gene. There is no efficient treatment for this serious and disabling disease. We established a combination method to detect carriers and perform prenatal diagnosis. Methods: In our study, from 1994 to 2005, using a different combination of 5 methods, including SRY gene amplification, multiplex PCR, multiplex Fluorescence PCR capillary electrophoresis, multiplex ligation-dependent probe amplification (MLPA) and linkage analysis of short tandem repeats (STR), 36 prenatal diagnosis were performed for pregnancies at risk of having a DMD/BMD baby through amniocentesis. Results: Fourteen out of 21 male fetuses were found to be affected and respective pregnancies were terminated. A combined diagnostic rate of 83% was achieved for 30 cases with deletions, duplications, and non-deletion mutations after tested by more than one method. Conclusion: Using a combined method, we can diagnoses patients and carriers in DMD families, and perform prenatal diagnosis for the risk fetus. MLPA provides a simple, rapid and accurate method for deletions and duplications of all the 79 DMD exons. MLPA method for DMD diagnosis is the first report in our country.
